A rapid identification of hit molecules for target proteins via physico-chemical descriptors

文献情報

出版日 2013-04-11

DOI 10.1039/C3CP44697B

インパクトファクター 3.676

著者

Goutam Mukherjee

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要旨

We report here a novel computationally fast protocol (RASPD) for identifying good candidates for any target protein from any molecule/million molecule database. A QSAR-type equation sets up the extent of complementarity of the physico-chemical properties of the target protein and the candidate molecule and an estimate of the binding energy is generated. A correlation coefficient of 0.84 and an average error ±1.45 kcal mol−1 are obtained for the calculated protein–ligand binding energies against experiment for more than 380 protein–ligand complexes. RASPD is seen to perform better than other popular scoring functions in predicting binding energies. The most interesting feature of this methodology is that it takes only a fraction of a second for calculating the binding energy of any ligand without docking in the active site of the target protein as opposed to several minutes for regular docking and scoring methods, while the accuracy in sorting good candidates remains comparable to that of conventional techniques. An entire million compound library, a (∼105 compound) natural product library and a (∼105 compound) NCI database can be scanned against a specified target protein within a few minutes for identifying hit molecules. The RASPD methodology is freely accessible at http://www.scfbio-iitd.res.in/software/drugdesign/raspd2.jsp.

掲載誌

Physical Chemistry Chemical Physics

CiteScore: 5.5

自己引用率: 10.3%

年間論文数: 3036

Physical Chemistry Chemical Physics (PCCP) is an international journal co-owned by 19 physical chemistry and physics societies from around the world. This journal publishes original, cutting-edge research in physical chemistry, chemical physics and biophysical chemistry. To be suitable for publication in PCCP, articles must include significant innovation and/or insight into physical chemistry; this is the most important criterion that reviewers and Editors will judge against when evaluating submissions. The journal has a broad scope and welcomes contributions spanning experiment, theory, computation and data science. Topical coverage includes spectroscopy, dynamics, kinetics, statistical mechanics, thermodynamics, electrochemistry, catalysis, surface science, quantum mechanics, quantum computing and machine learning. Interdisciplinary research areas such as polymers and soft matter, materials, nanoscience, energy, surfaces/interfaces, and biophysical chemistry are welcomed if they demonstrate significant innovation and/or insight into physical chemistry. Joined experimental/theoretical studies are particularly appreciated when complementary and based on up-to-date approaches.