Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.16 (HIV-1 protease)
 2,107 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A molecular dynamics method has been developed to describe the structural and dynamic properties of protein-ligand complexes that are truncated to their active sites. The active site is comprised of the ligand and discontinuous, positionally unrestrained peptide chains. This truncated active-site complex is surrounded by big unspecific pseudo-particles representing the complete protein and the solvent. Thus, knowledge of the folding of the outer parts of the protein is not required, and the method can be applied to protein models, derived from homology modeling. The method has been tested using ligand complexes of adenylate kinase, retinol binding protein, HIV-1 protease, and human leucocyte antigen. Comparisons with their crystal structures and with results from time-demanding simulations of the whole complexes in explicit water solvent show that the ligand binding properties are conserved. Most of the hydrogen bonds between the ligand and the active-site residues are reproduced and, furthermore, the simulation time is reduced.
 ...
PMID:A pseudo-particle approach for studying protein-ligand models truncated to their active sites. 872 31

The possibility of accurately describing the internal dynamics of proteins, in terms of movements of a few approximately-rigid subparts, is an appealing biophysical problem with important implications for the analysis and interpretation of data from experiments or numerical simulations. The problem is tackled here by means of a novel variational approach that exploits information about equilibrium fluctuations of interresidues distances, provided, e.g., by atomistic molecular dynamics simulations or coarse-grained models. No contiguity in primary sequence or in space is enforced a priori for amino acids grouped in the same rigid unit. The identification of the rigid protein moduli, or dynamical domains, provides valuable insight into functionally oriented aspects of protein internal dynamics. To illustrate this point, we first discuss the decomposition of adenylate kinase and HIV-1 protease and then extend the investigation to several representatives of the hydrolase enzymatic class. The known catalytic site of these enzymes is found to be preferentially located close to the boundary separating the two primary dynamical subdomains.
 ...
PMID:Coarse-grained description of protein internal dynamics: an optimal strategy for decomposing proteins in rigid subunits. 1952 59