Premium
Comparison of generalized born and poisson models: Energetics and dynamics of HIV protease
Author(s) -
David Laurent,
Luo Ray,
Gilson Michael K.
Publication year - 2000
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/(sici)1096-987x(200003)21:4<295::aid-jcc5>3.0.co;2-8
Subject(s) - hiv 1 protease , poisson distribution , molecular dynamics , human immunodeficiency virus (hiv) , statistical physics , nanosecond , active site , physics , chemistry , energetics , computational chemistry , protease , thermodynamics , mathematics , quantum mechanics , biology , nuclear magnetic resonance , statistics , laser , immunology , enzyme
This study characterizes the accuracy of energies and forces computed with a generalized Born (GB) model and the distance‐dependent dielectric (DDD) model with respect to detailed finite solutions of the Poisson equation (FDPE). Tests are done for a small molecule in solution and for HIV‐1 protease with inhibitor, KNI‐272. GB agrees well with FDPE for the small molecule, but less well for the protein system. The correlation between GB and FDPE energies is poorest in calculations of changes upon binding. Also, forces computed with the GB model are less accurate than energies. The DDD model is far less accurate than GB. Nanosecond stochastic dynamics simulations of HIV‐1 protease with an empty active site are used to examine the consequence of the models for the conformational preferences of the active site. Interestingly, the active site flaps remain near their starting conformations in the FDPE and GB simulations but collapse into the active site in the DDD simulation. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 295–309, 2000