Biomedical subjects

Chia-En Chang

Publications and source records attributed to Chia-En Chang.

3 recordsLinked to original sources

PubMed2004

Free energy, entropy, and induced fit in host-guest recognition: calculations with the second-generation mining minima algorithm.

This study applies a novel computational method to study molecular recognition for three sets of synthetic hosts: molecular clips, molecular tweezers, and a synthetic barbiturate receptor. The computed standard free energies of binding for the 12 binding reactions agree closely with experiment and provide insight into the roles of configurational entropy, preorganization, and induced fit in the systems studied. The computed changes in configurational entropy are comparable in magnitude to the changes in mean potential plus solvation energy, and they result primarily from changes in the average width of the energy wells upon binding. A strong correlation is observed between the changes in configurational energy and configurational entropy upon binding, resulting in near-linear compensation analogous to classical entropy-enthalpy compensation.

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PubMed2004

Calculation of cyclodextrin binding affinities: energy, entropy, and implications for drug design.

The second generation Mining Minima method yields binding affinities accurate to within 0.8 kcal/mol for the associations of alpha-, beta-, and gamma-cyclodextrin with benzene, resorcinol, flurbiprofen, naproxen, and nabumetone. These calculations require hours to a day on a commodity computer. The calculations also indicate that the changes in configurational entropy upon binding oppose association by as much as 24 kcal/mol and result primarily from a narrowing of energy wells in the bound versus the free state, rather than from a drop in the number of distinct low-energy conformations on binding. Also, the configurational entropy is found to vary substantially among the bound conformations of a given cyclodextrin-guest complex. This result suggests that the configurational entropy must be accounted for to reliably rank docked conformations in both host-guest and ligand-protein complexes. In close analogy with the common experimental observation of entropy-enthalpy compensation, the computed entropy changes show a near-linear relationship with the changes in mean potential plus solvation energy.

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PubMed2003

Tork: Conformational analysis method for molecules and complexes.

A conformational search method for organic molecules and bimolecular complexes is presented. The method, termed Tork, uses normal-mode analysis in bond-angle-torsion coordinates and focuses on a key subset of torsional coordinates to identify natural molecular motions that lead the initial conformation to new energy minima. New conformations are generated via distortion along these modes and their pairwise combinations, followed by energy minimization. For complexes, special treatment is accorded to the six coordinates that specify the position and orientation of one molecule relative to the other. Tests described here show that Tork is highly efficient for cyclic, acyclic, and mixed single molecules, as well as for host-guest complexes.

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