LowModeMD--implicit low-mode velocity filtering applied to conformational search of macrocycles and protein loops.
We present a method for conformational search of complex molecular systems such as macrocycles and protein loops. The method is based on perturbing an existing conformation along a molecular dynamics trajectory using initial atomic velocities with kinetic energy concentrated on the low-frequency vibrational modes, followed by energy minimization. A novel Chebyshev polynomial filter is used to heavily dampen the high-frequency components of a randomly generated Maxwell-Boltzmann velocity vector. The method is very efficient, even for large systems; it is straightforward to implement and requires only standard force-field energy and gradient evaluations. The results of several computational experiments suggest that the method is capable of efficiently sampling low-strain energy conformations of complex systems with nontrivial nonbonded interaction networks.
Labute
Paul
P
Chemical Computing Group, Inc., 1010 Sherbrooke St. W., Suite 910, Montreal H3A 2R7, Quebec, Canada. paul@chemcomp.com
D000818:Animals; D002417:Cattle; D047028:Macrocyclic Compounds / Q000737:chemistry*; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation / Q000191:economics; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D054460:rho-Associated Kinases / Q000737:chemistry
D047028:Macrocyclic Compounds; D011506:Proteins; D054460:rho-Associated Kinases