ISSN:0006-3525    

DOI:10.1002/bip.360320102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractA general formula is derived for the relation between the pair correlation function and the histogram of interparticle distances in small nonuniform systems. The formula is applied to random packings of spheres in a spherical container, which are generated by a Monte Carlo method. When measured properly, the resultant correlation functions are very similar to ones in bulk systems with the same volume fraction of particles. In contrast, the density is very nonuniform as a function of distance from the center of the container. The variation is an order of magnitude for the number density of particle centers, or several fold for the occupied volume fraction. It is described how these results can be used to analyze the forces that determine protein structure.

ISSN:0006-3525    

DOI:10.1002/bip.360320103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractA knowledge‐based three‐dimensional model of an anti‐insulin antibody, 125, was constructed using the structures of conserved residues found in other known crystallographic immunoglobulins. Molecular modeling and mechanics were done with the 125 amino acid sequences using QUANTA and CHARMm on a Silicon Graphics 4D70GT workstation. A minimal model was made by scaffolding using crystallography coordinates of the antibody HyHEL‐5, because it had the highest amino acid sequence homology with 125 (84% light chain, 65% heavy chain). The three hypervariable loop turns that are longer in 125 than in HyHEL‐5 (L1, L3, and H3) were modeled separately and incorporated into the HyHEL‐5 structure; then other amino acid substitutions were made and torsions optimized. The 125 model maintains all the structural attributes of an antibody and the structures conserved in known antibodies. Although there are many polar amino acids (especially serines) in this site, the overall van der Waals surface shape is determined by positions of aromatic side chains. Based on this model, it is suggested that hydrogen bonding may be key in the interaction between the human insulin A chain loop antigenic epit

ISSN:0006-3525    

DOI:10.1002/bip.360320104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractMolecular dynamics at 300 K was used as a conformation searching tool to analyze a knowledge‐based structure prediction of an anti‐insulin antibody. Solvation effects were modeled by packing water molecules around the antigen binding loops. Some loops underwent backbone and side‐chain conformational changes during the 95‐ps equilibration, and most of these new, lower potential energy conformations were stable during the subsequent 200‐ps simulation. Alterations to the model include changes in the intraloop, main‐chain hydrogen bonding network of loop H3, and adjustments of Tyr and Lys side chains of H3 induced by hydrogen bonding to water molecules. The structures observed during molecular dynamics support the conclusion of the previous paper that hydrogen bonding will play the dominant role in antibody‐insulin recognition. Determination of the structure of the antibody by x‐ray crystallography is currently being pursued to provide an experimental test of these results. The simulation appears to improve the model, but longer simulations at higher temperatures shou

ISSN:0006-3525    

DOI:10.1002/bip.360320105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractAn extended simulated annealing process (ESAP) has been developed in order to obtain an ensemble of conformations of a peptide segment from a protein fluctuating at a given temperature. The annealing process was performed with a fast Monte Carlo method using the scaled collective variables developed by Noguti and Gō. The system was divided into two parts: one consists of one or more peptide segments and is flexible around the main‐chain and side‐chain torsional angles; the other represents the rest of the molecule and was maintained fixed at the atomic positions determined by x‐ray experiments. The target function included the nonbonding atomic interactions and a distance function to anchor the N and C terminal ends of each segment to the fixed part. Three systems of complementary determining regions (CDR) of antibodies were tested and compared to x‐ray data: L2 loop (7 residues) of the light chain of α‐type Bence‐Jones protein, H1 and the H2 loops (14 residues) of McPC603, and H1 and H2 loops (12 residues) of HyHEL‐5. Each state of CDR conformations was characterized at room temperature by the average of their coordinates (average conformation) and the internal energy. With a limited number of annealing processes (10), starting from the extended conformation, we have obtained states with conformations close to the observed x‐ray structures, from 1.1 to 1.7 Å root mean square deviation (rmsd) of main‐chain atoms depending on the system. These states were identical or within 0.25 Å rmsd of those of lowest internal energy. For unknown CDR structures the criteria of lowest internal energies from ESAP can be used to predict hypervariable loop structures in antibodies with an accuracy compar

ISSN:0006-3525    

DOI:10.1002/bip.360320106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe solution structure of the photodimercis,syn‐dUp [ ]dT is derived with the aid of the genetic algorithm. The conformational space available for the molecule is sampled efficiently using the computer program DENISE and tested against a set of constraints available from nmr experiments. The dominant conformation in solution found with this approach can be described by the following combinations of sugar‐phosphate backbone torsion angles: ε (t), ζ(t), α(+), β(–ac), and γ(t). The conformation of the sugars and glycosidic torsion angles are S type andsyn, respectively. The cyclobutane ring and pyrimidines are puckered. In addition, other conformations that exist in equilibrium with the first are found. It is concluded that the cyclobutane‐pyrimidine system is rigid, whereas the sugar‐phosphate backbone is flexible. The solution structures are compared with the crystal structure of the strongly related cyano‐ethyl ester ofc

ISSN:0006-3525    

DOI:10.1002/bip.360320107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe quantum yield for cyclobutyl‐pyrimidine dimerization in DNA has been observed to increase approximately linearly with increasing pyrimidine tract length. A model without adjustable parameters for this yield is proposed based on energy delocalization, vibronic symmetry switching, and saturation statistics that describe the average number of (base pairwise) breathing modes in a given tract of pyrimidines. This average number of modes is an approximately linear function of the tract length. Monte Carlo techniques are used to simulate base sequences and photochemical events, and indicate that this model is consistent with experiment forTetrahymena pyriformisDN

ISSN:0006-3525    

DOI:10.1002/bip.360320108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe analysis of the factors that control the helical folding of Aib‐rich peptides is extended to include sensitivity to sequence patterns, and in particular the presence of contiguous non‐Aib α‐mono‐alkylated residues. The distinct hydrogen‐bonding network of the 310−helix, as contrasted with that of the competing α‐helical structure, is explicitly incorporated into a theoretical model for the 310−helix/α‐helix equilibrium constant for a given peptide. Finite length effects and the “extra” intrahelical hydrogen bond of the 310form are expressed naturally as a result of this loop analysis. This semiempirical model captures all the established features of existing empirical rules for helical conformational transitions in Aib‐rich sequences, as well as the recently detected helical transition induced sole

ISSN:0006-3525    

DOI:10.1002/bip.360320109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe cationic dye auramine O forms a fluorescent complex with Ca2+‐liganded calmodulin. One moderately strong binding site is present, as well as one or more weaker sites. The binding site for auramine O is different from those for toluidinyl‐naphthalene sulfonate. The dependence of binding upon electrolyte concentration suggests a substantial electrostatic component of the free energy of binding. The splitting of the bond between residues 77 and 78 by trypsin digestion abolishes auramine O binding; the N‐ and C‐terminal half‐molecules have virtually no binding capacity. This suggests that the primary binding site is located near the midpoint of the connecting strand and includes elements of both half‐molecules. Thrombin digestion, which splits calmodulin between residues 106 and 107, also substantially reduces auramine O binding; this may be interpreted in terms of the stabilization of the structure of the connecting strand by interaction with residues within binding domain IV. The binding affinity at pH 5.0, where the helical organization of the connecting strand may be intact, is greater than at

ISSN:0006-3525    

DOI:10.1002/bip.360320110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe interactions between the positively charged neuropeptides substance P (SP), bradykinin (BK), and zwitterionic Met‐enkephalin (ME) neuropeptides, and negatively charged SDS and zwitterionic lysophosphatidylcholine (LPC) membrane model systems, have been investigated using one‐ and two–dimensional nmr experiments. Proton longitudinal relaxation studies were used to characterize these interactions as intrinsic or extrinsic. An extrinsic interaction are similar to those observed for extrinsic membrane proteins. An intrinsic interaction are similar to those observed for intrinsic membrane proteins, and would require that the hydrophobic residues penetrate or insert into the hydrophobic core of the membrane. The interactions between both SP and BK and SDS, based on nmr results, may be characterized as intrinsic, and the interaction between ME and SDS may be characterized as extrinsic. Two–dimensional nuclear Overhauser enhancement spectroscopy experiments proved the insertion of the phenylalanine residues on both SP and BK into the hydrophobic core of SDS micelles. The interaction between SP and BK with LPC based on nmr results are characterized as extrinsic, with the interaction between ME and SDS characterized as weakly in

ISSN:0006-3525    

DOI:10.1002/bip.360320111

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY