Article
Direct Estimation of Entropy Loss Due to Reduced Translational and Rotational Motions upon Molecular Binding
Biopolymers
(2005)
Abstract
The entropic cost due to the loss of translational and rotational (T–R) degree of freedom upon binding has been well recognized for several decades. Tightly bound ligands have higher entropic costs than loosely bound ligands. Quantifying the ligand's residual T–R motions after binding, however, is not an easy task. We describe an approach that uses a reduced Hessian matrix to estimate the contributions due to translational and rotational degrees of freedom to entropy change upon molecular binding. The calculations use a harmonic model for the bound state but only include the T–R degrees of freedom. This approximation significantly speeds up entropy calculations because only 6 × 6 matrices need to be treated, which makes it easier to be used in computer‐aided drug design for studying many ligands. The methodological connection with other methods is discussed as well. We tested this approximation by applying it to study the binding of ATP, peptide inhibitor (PKI), and several bound water molecules to protein kinase A (PKA). These ligands span a wide range in size. The model gave reasonable estimates of the residual T–R entropy of bound ligands or water molecules. The residual T–R entropy demonstrated a wide range of values, e.g., 4 to 16 cal/K·mol for the bound water molecules of PKA.
Keywords
- translational and rotational entropy loss,
- molecular binding,
- reduced Hessian matrix,
- bound water
Disciplines
Publication Date
May 12, 2005
DOI
10.1002/bip.20344
Citation Information
Benzhuo Lu and Chung F. Wong. "Direct Estimation of Entropy Loss Due to Reduced Translational and Rotational Motions upon Molecular Binding" Biopolymers Vol. 79 Iss. 5 (2005) p. 277 - 285 Available at: http://works.bepress.com/chung-wong/37/