Journal
CHEMMEDCHEM
Volume 3, Issue 6, Pages 885-897Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.200700319
Keywords
computer-aided molecular design; docking; HYDE; scoring functions; virtual screening
Categories
Ask authors/readers for more resources
We developed a new empirical scoring function, HYDE, for the evaluation of protein-ligand complexes. HYDE estimates binding free energy based on two terms for dehydration and hydrogen bonding only. The essential feature of this scoring function is the integrated use of log P-derived atomic increments for the prediction of free dehydration energy and hydrogen bonding energy. Taking the dehydration of atoms within the interface into account shows that some atoms contribute favorably to the overall score, while others contribute unfavorably. For instance, hydrogen bond functions ore penalized if they are dehydrated unless they con overcompensate this loss by forming a hydrogen bond with excellent geometry. The main stabilizing contribution represents the removal of apolar groups from the water: the hydrophobic effect. Initial studies using the DUD dataset show that with HYDE, there is a significant decrease in false positives, a reasonable categorization of compounds as either non-binders, weak, medium or strong binders, and in particular, there is a generally applicable and thermodynamically sensible cutoff score below which there is a high likelihood that the compound is indeed a binder.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available