This research aims to further develop the capabilities of a new computer simulation technique that significantly enhances the scope and versatility of usual molecular dynamics simulations. Three general directions will be explored: (i) Determination of structure of small peptides. Structure of peptides (when existent) are of significant interest. Many peptides transfer signals to receptors and investigation of their conformations may lead to the design of substitutes. Furthermore, structure of short peptides may suggest initiation site for the process of protein folding. Presence of peptide segments with high probability for a unique structure may accelerate considerably the folding process. (ii) Refinement of low resolution protein structure. Nowadays the capabilities of computational methods that are based on statistical approaches are steadily increased. Nevertheless, so far the structure obtained are of low resolution. The combination of """"""""low resolution"""""""" global search methods and atomic detail refinement procedures based on LES is a promising approach. (iii) Extension of molecular dynamics time scales. The LES provides considerably more statistics for sampling molecular events. For dynamics LES is a mean field approximation. However, with a binary collision correction developed by us the LES describes diffusion quantitatively and will be employed to study ligand escapes from a protein matrix on the tens of nanoseconds time scale, a time scale that was not accessible to molecular dynamics before.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM041905-06A1
Application #
2181115
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1989-07-01
Project End
1997-06-30
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Hebrew University of Jerusalem
Department
Type
DUNS #
600044978
City
Jerusalem
State
Country
Israel
Zip Code
91904
Schueler-Furman, O; Elber, R; Margalit, H (1998) Knowledge-based structure prediction of MHC class I bound peptides: a study of 23 complexes. Fold Des 3:549-64
Mohanty, D; Elber, R; Thirumalai, D et al. (1997) Kinetics of peptide folding: computer simulations of SYPFDV and peptide variants in water. J Mol Biol 272:423-42
Keasar, C; Elber, R; Skolnick, J (1997) Simultaneous and coupled energy optimization of homologous proteins: a new tool for structure prediction. Fold Des 2:247-59
Simmerling, C L; Elber, R (1995) Computer determination of peptide conformations in water: different roads to structure. Proc Natl Acad Sci U S A 92:3190-3
Carlson, M L; Regan, R; Elber, R et al. (1994) Nitric oxide recombination to double mutants of myoglobin: role of ligand diffusion in a fluctuating heme pocket. Biochemistry 33:10597-606
Chiancone, E; Elber, R; Royer Jr, W E et al. (1993) Ligand binding and conformation change in the dimeric hemoglobin of the clam Scapharca inaequivalvis. J Biol Chem 268:5711-8
Li, H; Elber, R; Straub, J E (1993) Molecular dynamics simulation of NO recombination to myoglobin mutants. J Biol Chem 268:17908-16
Gibson, Q H; Regan, R; Elber, R et al. (1992) Distal pocket residues affect picosecond ligand recombination in myoglobin. An experimental and molecular dynamics study of position 29 mutants. J Biol Chem 267:22022-34
Czerminski, R; Elber, R (1991) Computational studies of ligand diffusion in globins: I. Leghemoglobin. Proteins 10:70-80