We present a novel and efficient approach for finding various fragment-binding poses to a protein using MD simulation. In general, a long-time or biased MD is required to get possible binding variations in the conventional approaches. Our approach adopts random exchange non-bonding function (RE-NBF) method. In this approach, protein replicas with high concentration of fragments have different non-bonding potential functions from each other, and the replicas are randomly exchanged in a short cycle time. We applied this approach to human coagulation factor Xa with 2.4 M concentration of 6-chloro-1-benzothiophene-2-ol, and found that fragment molecules bound to protein pocket 60 times during a 10-ns MD simulation. This indicates that our approach provides a sufficient number of fragment-binding poses through a short-time MD simulation.

Efficient approach for finding fragment-binding poses

255th National Meeting (2018)

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