96413616 0008816770 1996 11 13 1996 11 13

0027-8424 93 19 1996 Sep 17 Packing at the protein-water interface. 10167-72 We have determined the packing efficiency at the protein-water interface by calculating the volumes of atoms on the protein surface and nearby water molecules in 22 crystal structures. We find that an atom on the protein surface occupies, on average, a volume approximately 7% larger than an atom of equivalent chemical type in the protein core. In these calculations, larger volumes result from voids between atoms and thus imply a looser or less efficient packing. We further find that the volumes of individual atoms are not related to their chemical type but rather to their structural location. More exposed atoms have larger volumes. Moreover, the packing around atoms in locally concave, grooved regions of protein surfaces is looser than that around atoms in locally convex, ridge regions. This as a direct manifestation of surface curvature-dependent hydration. The net volume increase for atoms on the protein surface is compensated by volume decreases in water molecules near the surface. These waters occupy volumes smaller than those in the bulk solvent by up to 20%; the precise amount of this decrease is directly related to the extent of contact with the protein. Department of Structural Biology, Stanford University, CA 94305, USA. Gerstein M Chothia C Eng JOURNAL ARTICLE

UNITED STATES Proc Natl Acad Sci U S A PV3 0 Enzymes 0 Proteins 7732-18-5 Water IM Animal Binding Sites Crystallography, X-Ray Enzymes chemistry Hydrogen Bonding Models, Structural Protein Conformation Protein Structure, Secondary Proteins chemistry Support, Non-U.S. Gov't Surface Properties Water http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8816770&dopt=Abstract http://bioinfo.mbb.yale.edu/e-print/surfpack-pnas/text.pdf 97031580 0008877505 1997 01 30 1997 01 30

4 1996 Using iterative dynamic programming to obtain accurate pairwise and multiple alignments of protein structures. 59-67 We show how a basic pairwise alignment procedure can be improved to more accurately align conserved structural regions, by using variable, position-dependent gap penalties that depend on secondary structure and by taking the consensus of a number of suboptimal alignments. These improvements, which are novel for structural alignment, are direct analogs of what is possible with normal sequences alignment. They are feasible for us since our basic structural alignment procedure, unlike others, is so similar to normal sequence alignment. We further present preliminary results that show how our procedure can be generalized to produce a multiple alignment of a family of structures. Our approach is based on finding a "median" structure from doing all possible pairwise alignments and then aligning everything to it. Department of Structural Biology, Stanford University CA 94305, USA. mbg@hyper.stanford.edu Gerstein M Levitt M Eng JOURNAL ARTICLE

UNITED STATES Ismb CCP EC 1.5.1.3 Tetrahydrofolate Dehydrogenase 9004-22-2 Globin IM Amino Acid Sequence Globin chemistry Models, Molecular Molecular Sequence Data Protein Conformation Protein Structure, Secondary Sequence Alignment Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Tetrahydrofolate Dehydrogenase chemistry http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8877505&dopt=Abstract http://bioinfo.mbb.yale.edu/hyper/mbg/AvgCore/ismb96/ 96404302 0008808580 1996 10 25 1996 10 25

0266-7061 11 6 1995 Dec Using a measure of structural variation to define a core for the globins. 633-44 As the database of three-dimensional protein structures expands, it becomes possible to classify related structures into families. Some of these families, such as the globins, have enough members to allow statistical analysis of conserved features. Previously, we have shown that a probabilistic representation based on means and variances can be useful for defining structural cores for large families. These cores contain the subset of atoms that are in essentially the same relative positions in all members of the family. In addition to defining a core, our method creates an ordered list of atoms, ranked by their structural variation. In applying our core-finding procedure to the globins, we find that helices A, B, G and H form a structural core with low variance. These helices fold early in the folding pathway, and superimpose well with helices in the helix-turn-helix repressor protein family. The non-core helices (F and the parts of other helices that interact with it) are associated with the functional differences among the globins, and are encoded within a separate exon. We have also compared the variability measure implicit in our core structures with measures of sequence variability, using a procedure for measuring sequence variability that helps correct for the biased sampling in the databanks. We find, somewhat surprisingly, that sequence variation does not appear to correlate with structural variation. Department of Structural Biology, Fairchild D109, Stanford University, CA 94305, USA. Gerstein M Altman RB Eng LM-05652 LM NLM LM-05305 LM NLM JOURNAL ARTICLE

ENGLAND Comput Appl Biosci CAB 9004-22-2 Globin IM Algorithms Amino Acid Sequence Animal Globin chemistry genetics Human Models, Molecular Molecular Sequence Data Molecular Structure Protein Structure, Secondary Sequence Homology, Amino Acid Software Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Variation (Genetics) http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8808580&dopt=Abstract 96351873 0008749848 1996 10 10 1996 10 10

0887-3585 23 4 1995 Dec Binding geometry of alpha-helices that recognize DNA. 525-35 Many transcription factors have an alpha-helix that binds to DNA bases in a specific fashion. The DNA-binding geometry of these recognition helices varies substantially. We define a set of parameters to describe the binding geometry of recognition helices and analyze specific stereochemical elements that determine particular geometries. Because the convex surface of the helix must fit into the concave surface of the DNA major groove, the number of degrees of freedom of the recognition helix is reduced from a possible six to a single angle, which we call alpha. The chemically interacting DNA bases and amino acid residues must lie along a common line and have the same spacing along it. This pairing of base positions with residue positions seems to restrict the binding geometry further to a set of discrete values for alpha. MRC Laboratory of Molecular Biology, Cambridge, United Kingdom. Suzuki M Gerstein M Eng JOURNAL ARTICLE

UNITED STATES Proteins PTS 0 Transcription Factors 9007-49-2 DNA IM Amino Acid Sequence Binding Sites Comparative Study Crystallography, X-Ray DNA chemistry metabolism Information Systems Models, Molecular Molecular Sequence Data Nucleic Acid Conformation Protein Structure, Secondary Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't Transcription Factors chemistry metabolism http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8749848&dopt=Abstract 95371108 0007643385 1995 09 18 1995 09 18

0022-2836 251 1 1995 Aug 4 Average core structures and variability measures for protein families: application to the immunoglobulins. 161-75 A variety of methods are currently available for creating multiple alignments, and these can be used to define and characterize families of related proteins, such as the globins or the immunoglobulins. We have developed a method for using a multiple alignment to identify an average structural "core", a subset of atoms with low structural variation. We show how the means and variances of core-atom positions summarize the commonalities and differences with a family, making them particularly useful in compiling libraries of protein folds. We show further how it is possible to describe the rotation and translation relating two core structures, as in two domains of a multi-domain protein, in a consistent fashion in terms of a "mean" transformation and a deviation about this mean. Once determined, our average core structures (with their implicit measure of structural variation) allow us to define a measure of structural similarity more informative than the usual root-mean-square (RMS) deviation in atomic position, i.e. a "better RMS." Our average structures also permit straightforward comparisons between variation in structure and sequence at each position in a family. We have applied our core-finding methodology in detail to the immunoglobulin family. We find that the structural variability we observe just within the VL and VH domains anticipates the variability that others have observed throughout the whole immunoglobulin superfamily; that a core definition based on sequence conservation, somewhat surprisingly, does not agree with one based on structural similarity; and that the cores of the VL and VH domains vary about 5 degrees in relative orientation across the known structures. Section on Medical Informatics, Stanford University, CA 94305, USA. Gerstein M Altman RB Eng LM-05652 LM NLM LM-05305 LM NLM JOURNAL ARTICLE

ENGLAND J Mol Biol J6V 0 Immunoglobulins 0 Proteins IM Algorithms Immunoglobulins chemistry Models, Molecular Molecular Structure Protein Conformation Proteins chemistry Sequence Alignment methods Statistics Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7643385&dopt=Abstract 95311318 0007540695 1995 07 27 1995 07 27 1995 12 01

0022-2836 249 5 1995 Jun 23 The volume of atoms on the protein surface: calculated from simulation, using Voronoi polyhedra. 955-66 We analyze the volume of atoms on the protein surface during a molecular-dynamics simulation of a small protein (pancreatic trypsin inhibitor). To calculate volumes, we use a particular geometric construction, called Voronoi polyhedra, that divides the total volume of the simulation box amongst the atoms, rendering them relatively larger or smaller depending on how tightly they are packed. We find that most of the atoms on the protein surface are larger than those buried in the core (by approximately 6%), except for the charged atoms, which decrease in size, presumably due to electroconstriction. We also find that water molecules are larger near apolar atoms on the protein surface and smaller near charged atoms, in comparison to "bulk" water molecules far from the protein. Taken together, these findings necessarily imply that apolar atoms on the protein surface and their associated water molecules are less tightly packed (than corresponding atoms in the protein core and bulk water) and the opposite is the case for charged atoms. This looser apolar packing and tighter charged packing fundamentally reflects protein-water distances that are larger or smaller than those expected from van der Waals radii. In addition to the calculation of mean volumes, simulations allow us to investigate the volume fluctuations and hence compressibilities of the protein and solvent atoms. The relatively large volume fluctuations of atoms at the protein-water interface indicates that they have a more variable packing than corresponding atoms in the protein core or in bulk water. We try to adhere to traditional conventions throughout our calculations. Nevertheless, we are aware of and discuss three complexities that significantly qualify our calculations: the positioning of the dividing plane between atoms, the problem of vertex error, and the choice of atom radii. In particular, our results highlight how poor a "compromise" the commonly accepted value of 1.4 A is for the radius of a water molecule. Department of Structural Biology, Standford University, CA 94305, USA. Gerstein M Tsai J Levitt M Eng GM 41455 GM NIGMS JOURNAL ARTICLE

ENGLAND J Mol Biol J6V 7732-18-5 Water 9087-70-1 Aprotinin IM Animal Aprotinin chemistry Cattle Computer Simulation Models, Molecular Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Surface Properties Water chemistry http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7540695&dopt=Abstract http://bioinfo.mbb.yale.edu/hyper/mbg/SurfaceVolumes/ 96047471 0007567918 1995 11 14 1995 11 14

0269-2139 8 4 1995 Apr DNA recognition and superstructure formation by helix-turn-helix proteins. 329-38 The way helix-turn-helix proteins recognize DNA is analysed by comparing their sequences, structures, and binding specificities. Individual recognition helices in these proteins bind to four DNA base pairs with the same geometry. However, pairs of recognition helices in the protein dimers can have different separations and orientations. These differences are used for discriminating between DNAs which have different superstructures, in particular, different numbers of base pairs between sets of the four base pairs. MRC Laboratory of Molecular Biology, Cambridge, UK. Suzuki M Yagi N Gerstein M Eng JOURNAL ARTICLE

ENGLAND Protein Eng PR1 0 DNA-Binding Proteins 0 Transcription Factors 9007-49-2 DNA IM Amino Acid Sequence Base Sequence Binding Sites DNA chemistry metabolism DNA-Binding Proteins chemistry metabolism Helix-Turn-Helix Motifs Molecular Sequence Data Nuclear Magnetic Resonance Nucleic Acid Conformation Protein Structure, Secondary Support, Non-U.S. Gov't Transcription Factors chemistry metabolism http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7567918&dopt=Abstract 96047470 0007567917 1995 11 14 1995 11 14

0269-2139 8 4 1995 Apr DNA recognition code of transcription factors. 319-28 MRC Laboratory of Molecular Biology, Cambridge, UK. Suzuki M Brenner SE Gerstein M Yagi N Eng JOURNAL ARTICLE REVIEW REVIEW, TUTORIAL

ENGLAND Protein Eng PR1 0 Transcription Factors 9007-49-2 DNA IM Amino Acid Sequence Animal Base Sequence Binding Sites DNA chemistry metabolism Human Molecular Sequence Data Nucleic Acid Conformation Protein Structure, Secondary Support, Non-U.S. Gov't Transcription Factors chemistry metabolism 101 http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7567917&dopt=Abstract 94359814 0008078776 1994 10 03 1994 10 03

0305-1048 22 16 1994 Aug 25 Stereochemical basis of DNA recognition by Zn fingers. 3397-405 DNA-recognition rules for Zn fingers are discussed in terms of crystal structures. The rules can explain the DNA-binding characteristics of a number of Zn finger proteins for which there are no crystal structures. The rules have two parts: chemical rules, which list the possible pairings between the 4 DNA bases and the 20 amino acid residues, and stereochemical rules, which describe the specific base positions contacted by several amino acid positions in the Zn finger. It is discussed that to maintain the correct binding geometry, in which the N-terminus of the recognition helix is closer to the DNA than the C-terminus, the residues facing the DNA on the helix must be larger near the C-terminus, and that two different types of fingers (A and B) bind to DNA in distinctly different ways and cover different numbers of base pairs. MRC Laboratory of Molecular Biology, Cambridge, UK. Suzuki M Gerstein M Yagi N Eng JOURNAL ARTICLE

ENGLAND Nucleic Acids Res O8L 0 tramtrack protein 0 transcription factor TFIIIA 0 DNA-Binding Proteins 0 Krox-24 protein 0 Transcription Factors 7004-12-8 Arginine 9007-49-2 DNA IM Amino Acid Sequence Arginine metabolism Binding Sites Crystallization DNA chemistry metabolism DNA-Binding Proteins chemistry metabolism Molecular Sequence Data Nucleic Acid Conformation Protein Structure, Secondary Regulatory Sequences, Nucleic Acid Structure-Activity Relationship Transcription Factors chemistry metabolism Zinc Fingers http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8078776&dopt=Abstract 95006332 0007922041 1994 11 10 1994 11 10

0969-2126 2 7 1994 Jul 15 Volume changes on protein folding. 641-9 BACKGROUND: Protein volumes change very little on folding at low pressure, but at high pressure the unfolded state is more compact. So far, the molecular origins of this behaviour have not been explained: it is the opposite of that expected from the model of the hydrophobic effect based on the transfer of non-polar solutes from water to organic solvent. RESULTS: We redetermined the mean volumes occupied by residues in the interior of proteins. The new residue volumes are smaller than those given by previous calculations which were based on much more limited data. They show that the packing density in protein interiors is exceptionally high. Comparison of the volumes that residues occupy in proteins with those they occupy in solution shows that aliphatic groups have smaller volumes in protein interiors than in solution, while peptide and charged groups have larger volumes. The cancellation of these volume changes is the reason that the net change on folding is very small. CONCLUSIONS: The exceptionally high density of the protein interior shown here implies that packing forces play a more important role in protein stability than has been believed hitherto. Cambridge Centre for Protein Engineering, UK. Harpaz Y Gerstein M Chothia C Eng JOURNAL ARTICLE

ENGLAND Structure B31 0 Amino Acids 0 Peptides 0 Solutions IM Amino Acid Sequence Amino Acids chemistry Chemistry, Physical Comparative Study Mathematical Computing Models, Chemical Molecular Sequence Data Particle Size Peptides chemistry Protein Conformation Protein Folding Solutions chemistry Support, Non-U.S. Gov't Surface Properties http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7922041&dopt=Abstract http://bioinfo.mbb.yale.edu/e-print/volfold-structure/text.pdf 94263987 0008204609 1994 07 08 1994 07 08

0006-2960 33 22 1994 Jun 7 Structural mechanisms for domain movements in proteins. 6739-49 We survey all the known instances of domain movements in proteins for which there is crystallographic evidence for the movement. We explain these domain movements in terms of the repertoire of low-energy conformation changes that are known to occur in proteins. We first describe the basic elements of this repertoire, hinge and shear motions, and then show how the elements of the repertoire can be combined to produce domain movements. We emphasize that the elements used in particular proteins are determined mainly by the structure of the interfaces between the domains. Department of Haematology, Cambridge University, U.K. Gerstein M Lesk AM Chothia C Eng JOURNAL ARTICLE REVIEW REVIEW, ACADEMIC

UNITED STATES Biochemistry A0G 0 Proteins IM Motion Protein Structure, Secondary Protein Structure, Tertiary Proteins chemistry Support, Non-U.S. Gov't Thermodynamics 102 http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8204609&dopt=Abstract http://bioinfo.mbb.yale.edu/hyper/mbg/DomainClosure/ 94301993 0008029203 1994 08 08 1994 08 08

0269-2139 7 4 1994 Apr Solution structure of the DNA binding octapeptide repeat of the K10 gene product. 461-70 A putative transcription factor, the Drosophila K10 gene product, contains eight repeats of the octapeptide sequence SPNQQQHP or close variants. The solution structure of the K10 repeat was studied by NMR using a peptide composed of two SPNQQQHP units (referred to here as HP2). To overcome problems caused by degeneracy of backbone amide signals of Gln residues, a series of synthetic peptides containing an 15N-labelled main chain amide at different positions in HP2 were synthesized. In aqueous trifluoroethanol solution, HP2 folds into two structural units; the SPNQ part of each unit folds into a turn structure, while the C-terminal part shows some helical characteristics but is less structured. The N-terminal turn is likely to provide a core that produces a more stable helical structure upon binding to DNA and probably 'caps' the segmented helical unit at its N-terminus. This model is supported by a DNA footprinting study which shows that one SPNQQQHP unit spans four base pairs upon binding to A/T-rich sequences of DNA. MRC Laboratory of Molecular Biology, Cambridge, UK. Suzuki M Neuhaus D Gerstein M Aimoto S Eng JOURNAL ARTICLE

ENGLAND Protein Eng PR1 0 DNA-Binding Proteins 0 K10 protein 0 Nuclear Proteins 0 Peptide Fragments 0 Solutions 1438-30-8 Netropsin IM Amino Acid Sequence Animal Base Sequence Binding Sites Circular Dichroism Drosophila DNA-Binding Proteins chemistry Models, Molecular Molecular Sequence Data Netropsin metabolism Nuclear Magnetic Resonance Nuclear Proteins chemistry metabolism Peptide Fragments chemistry Protein Binding Solutions Support, Non-U.S. Gov't http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8029203 94166074 0008120887 1994 04 07 1994 04 07

0022-2836 236 4 1994 Mar 4 Volume changes in protein evolution. 1067-78 We have determined the variations in volume that occur during evolution in the buried core of three different families of proteins. The variation of the whole core is very small (approximately 2.5%) compared to the variation at individual sites (approximately 13%). However, by comparing our results to those expected from random sequences with no correlations between sites, we show that the small variation observed may simply be a manifestation of the statistical "law of large numbers" and not reflect any compensating changes in, or global constraints upon, protein sequences. We have also analysed in detail the volume variations at individual sites, both in the core and on the surface, and compared these variations with those expected from random sequences. Individual sites on the surface have nearly the same variation as random sequences (24% versus 28% variation). However, individual sites in the core have about half the variation of random sequences (13% versus 30%). Roughly, half of these core sites strongly conserve their volume (0 to 10% variation); one quarter have moderate variation (10 to 20%); and the remaining quarter vary randomly (20 to 40%). Our results have clear implications for the relationship between protein sequence and structure. For our analysis, we have developed a new and simple method for weighting protein sequences to correct for unequal representation, which we describe in an Appendix. MRC Laboratory of Molecular Biology, Cambridge, U.K. Gerstein M Sonnhammer EL Chothia C Eng JOURNAL ARTICLE

ENGLAND J Mol Biol J6V EC 1.5.1.3 Tetrahydrofolate Dehydrogenase 0 Proteins 12284-43-4 Azurin 9004-22-2 Globin 9014-09-9 Plastocyanin IM Algorithms Amino Acid Sequence Animal Azurin chemistry genetics Binding Sites genetics Evolution Globin chemistry genetics Human Models, Chemical Molecular Sequence Data Molecular Structure Plastocyanin chemistry genetics Protein Conformation Protein Folding Proteins chemistry genetics Support, Non-U.S. Gov't Tetrahydrofolate Dehydrogenase chemistry genetics Variation (Genetics) http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8120887&dopt=Abstract http://bioinfo.mbb.yale.edu/hyper/mbg/AvgCore/ 96038999 0007584390 1995 12 14 1995 12 14

2 1994 Finding an average core structure: application to the globins. 19-27 We present a procedure for automatically identifying from a set of aligned protein structures a subset of atoms with only a small amount of structural variation, i.e., a core. We apply this procedure to the globin family of proteins. Based purely on the results of the procedure, we show that the globin fold can be divided into two parts. The part with greater structural variation consists of the residues near the heme (the F helix and parts of the G and H helices), and the part with lesser structural variation (the core) forms a structural framework similar to that of the repressor protein (A, B, and E helices and remainder of the G and H helices). Such a division is consistent with many other structural and biochemical findings. In addition, we find further partitions within the core that may have biological significance. Finally, using the structural core of the globin family as a reference point, we have compared structural variation to sequence variation and shown that a core definition based on sequence conservation does not necessarily agree with one based on structural similarity. Section on Medical Informatics, Stanford University, CA 94305, USA. Altman RB Gerstein M Eng LM-05305 LM NLM JOURNAL ARTICLE

UNITED STATES Ismb CCP 9004-22-2 Globin IM Algorithms Amino Acid Sequence Animal Computer Simulation Globin chemistry Human Molecular Sequence Data Sequence Alignment Sequence Analysis Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7584390&dopt=Abstract http://bioinfo.mbb.yale.edu/hyper/mbg/ISMB-94-60/ 94047086 0008230220 1993 12 15 1993 12 15

0022-2836 234 2 1993 Nov 20 Domain closure in lactoferrin. Two hinges produce a see-saw motion between alternative close-packed interfaces. 357-72 Lactoferrin is an iron transport protein. Upon binding iron, the two domains in the N-terminal half of the molecule move together. Previous work has shown that this domain closure involves two hinges. Using the newly refined structure of the open form, the structural mechanism underlying this motion is analyzed here in detail. Upon closure the domains rotate 54 degrees essentially as rigid bodies. The axis of rotation passes through the two beta-strands linking the domains. These strands contain hinges in the sense that three large torsion angle changes are responsible for the bulk of the motion while smaller torsion angle changes in neighboring residues are responsible for the remainder of the motion. The rotation axes of these three torsion angle changes are nearly parallel to the axis of the overall 54 degrees rotation, so the local motion in the hinges can be directly related to the overall motion. A crucial feature of the hinge residues is that they have very few packing constraints on their main-chain atoms. The domains make different packing contacts with each other in the open and closed forms. These contacts form two interdomain interfaces arranged on either side of the hinges. Pivoting about the hinges produces a see-saw motion between the two interfaces. That is, when the domains close down, residues in the interface on one side of the hinges become buried and close-packed and residues on the other side become exposed. The situation is reversed when the domains open up. Lactoferrin provides a particularly clear example of the general features of hinged domain motion. It is compared to other instances of hinged domain closure and contrasted with instances of shear domain closure, where the overall motion is a summation of many small sliding motions between close-packed segments of polypeptide. MRC Laboratory of Molecular Biology, Cambridge, U.K. Gerstein M Anderson BF Norris GE Baker EN Lesk AM Chothia C Eng HD-20859 HD NICHD JOURNAL ARTICLE

ENGLAND J Mol Biol J6V 0 Lactoferrin IM Amino Acid Sequence Animal Human Lactoferrin chemistry Models, Molecular Molecular Sequence Data Motion Protein Conformation Protein Folding Protein Structure, Tertiary Sequence Homology, Amino Acid Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8230220&dopt=Abstract 94052067 0008234227 1993 12 08 1993 12 08

0269-2139 6 6 1993 Aug An NMR study on the DNA-binding SPKK motif and a model for its interaction with DNA. 565-74 The solution structure of one and two repeats of the 'SPKK' DNA-binding motif is reported on the basis of NMR measurements. In dimethylsulphoxide (DMSO) the major population (approximately 90%) of peptides, SPRKSPRK(S2) and GSPKKSPRK(S2b), adopts a conformation, which has two trans prolines. The two 'SP(R/K)K' units in these peptides are equivalent and each adopts a turn structure exchanging with an extended structure. This is suggested by an NOE connectivity of the beta-turn type, between the backbone amide protons of residues (i+2) and (i+3) and NOE connectivities of the Asx(sigma)-turn type, between protons of the ith Ser and the backbone amide proton on residue (i+2). This suggests that each SP(R/K)K unit has a structural intermediate between (or a combination of) a beta-turn and an Asx(sigma)-turn. In 90-10% DMSO/H2O at 4 degrees C the two units of S2 are connected more tightly by folding into a short 3(10) helix, broken at the second proline. For another peptide, Thr-Pro-Arg-Lys(T1), the major population (75%) in 100% DMSO comprises a beta-turn in rapid exchange with an extended structure. We did not observe an NOE connectivity of the Asx(sigma) type with the T1 peptide. A possible structure of the SPKK motif in the complex with DNA is discussed. MRC Laboratory of Molecular Biology, Cambridge, UK. Suzuki M Gerstein M Johnson T Eng JOURNAL ARTICLE

ENGLAND Protein Eng PR1 0 DNA-Binding Proteins 0 Peptide Fragments 9007-49-2 DNA IM Amino Acid Sequence Binding Sites Comparative Study DNA metabolism DNA-Binding Proteins chemistry metabolism Hydrogen Bonding Models, Molecular Molecular Sequence Data Nuclear Magnetic Resonance Nucleic Acid Conformation Peptide Fragments chemistry Protein Binding Protein Structure, Secondary Support, Non-U.S. Gov't http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8234227&dopt=Abstract 93217998 0008464069 1993 04 30 1993 04 30

0022-2836 230 2 1993 Mar 20 What is the natural boundary of a protein in solution? 641-50 At what distance do proteins in solution interact? Molecular simulation of water around two helices is used to address this question. Calculations are done with two ideal, parallel, polyalanine alpha-helices separated by 9 A, 11 A, 13 A, and 15 A. The second peak in the oxygen density (or loosely the second shell of water molecules) is used to define a hydration surface around the protein, which separates bulk solvent from water molecules strongly influenced by the protein. The hydration surface is contrasted with the Richards-Connolly molecular surface. It indicates that the helices are not completely separate until 15 A, while the molecular surface shows complete separation at 13 A. Suggesting shape-dependent aspects of hydration, the hydration surface only loosely follows the van der Waals outline of the protein surface. In particular, at the 9 A separation, the van der Waals envelopes of the helices make contact; two narrow crevices are formed on either side of the contact; and the water within the crevices is strongly localized in arrangements bridging the helices. A comparison of these 'normal' water simulations with a simulation of a simple, uncharged solvent highlights the importance of hydrogen bonding in structuring liquid water and further contrasts the molecular surface and the hydration surface. MRC Laboratory of Molecular Biology Hills Road, Cambridge, U.K. Gerstein M Lynden-Bell RM Eng JOURNAL ARTICLE

ENGLAND J Mol Biol J6V 0 Peptides 0 Proteins 0 Solutions 25191-17-7 polyalanine 7732-18-5 Water IM Calorimetry Models, Chemical Peptides chemistry Protein Structure, Secondary Proteins chemistry Solutions Support, Non-U.S. Gov't Water X-Ray Diffraction methods http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8464069&dopt=Abstract 93156056 0008429559 1993 03 11 1993 03 11

0022-2836 229 2 1993 Jan 20 Domain closure in adenylate kinase. Joints on either side of two helices close like neighboring fingers. 494-501 In large variants of adenylate kinase the AMP and ATP substrates are buried by a domain rotating by 90 degrees. Here conformational changes responsible for this domain closure are determined by an analysis of the open state of beef heart mitochondrial adenylate kinase and the closed state of Escherichia coli adenylate kinase. Although these two proteins have sequence differences, the principal structural changes responsible for the domain movements are large, and can clearly be distinguished from the effects of evolution. The mobile domain is linked to the rest of the protein by two helices packed together in an antiparallel fashion. During the closure, deformations take place in four localized regions, called joints, near the N and C termini of these helices. Three of these joints have simple motions that can be well approximated by rotations of three torsion angles, but the joint that makes contact with the ligand involves motion throughout an extended loop: i.e. two torsions on either side of a reverse turn change significantly. The main chain atoms of the joints have few packing constraints. The first pair of joints is responsible for approximately 30 degrees of the total rotation and the second pair for the remaining approximately 60 degrees. These movements carries along the regions between the joints, the two helices and the rest of the mobile domain, to a first approximation, as rigid bodies. This jointed domain closure mechanism is contrasted with the shear mechanisms found in other enzymes. MRC Laboratory of Molecular Biology, Cambridge, U.K. Gerstein M Schulz G Chothia C Eng JOURNAL ARTICLE

ENGLAND J Mol Biol J6V EC 2.7.4.3 Adenylate Kinase IM Adenylate Kinase chemistry metabolism Animal Cattle Computer Simulation Escherichia coli enzymology Mitochondria, Heart enzymology Models, Molecular Protein Conformation Support, Non-U.S. Gov't http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8429559&dopt=Abstract 93154310 0008428572 1993 03 10 1993 03 10

0261-4189 12 1 1993 Jan Electron diffraction analysis of structural changes in the photocycle of bacteriorhodopsin. 1-8 Structural changes are central to the mechanism of light-driven proton transport by bacteriorhodopsin, a seven-helix membrane protein. The main intermediate formed upon light absorption is M, which occurs between the proton release and uptake steps of the photocycle. To investigate the structure of the M intermediate, we have carried out electron diffraction studies with two-dimensional crystals of wild-type bacteriorhodopsin and the Asp96-->Gly mutant. The M intermediate was trapped by rapidly freezing the crystals in liquid ethane following illumination with a xenon flash lamp at 5 and 25 degrees C. Here, we present 3.5 A resolution Fourier projection maps of the differences between the M intermediate and the ground state of bacteriorhodopsin. The most prominent structural changes are observed in the vicinity of helices F and G and are localized to the cytoplasmic half of the membrane. MRC Laboratory of Molecular Biology, Cambridge, UK. Subramaniam S