Structure-Based Drug Design
This project’s goal is to develop and apply new computational methods for structure-based drug design. Previous studies led to the development of the cationic dummy atom approach for molecular dynamics simulations of metalloproteins such as the zinc endopeptidase of botulinum neurotoxin serotype A and the multiple molecular dynamics simulation method for prediction of protein structures as drug targets from genetic sequences and for prediction of synthetically-accessible drug candidates. The researchers are currently testing the practicality of their new methods in identification and optimization of small-molecule reactivators of human acetylcholinesterase and small-molecule inhibitors of the zinc endopeptidase of botulinum neurotoxin serotype A, insect acetylcholinesterases, and ribosome inactivating proteins. Successful completion of these projects will lead to new methods for just-in-time drug discovery and ultimately result in therapeutics for treating cancers, infectious diseases, and other medical problems.