Experimental-like affinity constants and enantioselectivity estimates from flexible docking.
Summary of "Experimental-like affinity constants and enantioselectivity estimates from flexible docking."
Experimental-like affinity constants and enantioselectivity estimates, not predicted so far computationally, were obtained using a novel flexible modelling/docking combined strategy. The S- and R-warfarin-Human serum albumin (HSA, Site I) complexes were used as an interaction model. The process for a verified estimation includes: (i) ionized open chain forms at physiological pH (a recent focus); (ii) conformational search (Molecular Mechanics and Monte Carlo methods); (iii) rigid protein-flexible ligand docking (GlideXP) generating low energy paired S- and R-poses; (iv) graphical comparison against the X-ray crystal structure (unsatisfactory verification step); (v) Quantum Polarized Ligand Docking (insufficient verification step); (vi) Induced Fit Docking (one pose satisfying the verification criterion; selection step); (vii) converting docking scores to affinity and enantioselectivity estimates (log KS = 5.43, log KR = 5.34, ES = KS / KR = 1.23) and numerical comparison against equivalent literature data from bio-analytical techniques (validation step); (viii) intermolecular forces explaining ES (hydrogen bonding and π-π interactions).
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Name: Journal of chemical information and modeling
Medical and Biotech [MESH] Definitions
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