Vol.:(0123456789) 1 3 Molecular Diversity https://doi.org/10.1007/s11030-020-10129-8 ORIGINAL ARTICLE Modeling and simulation study to identify threonine synthase as possible drug target in Leishmania major Rohan J. Meshram 1  · Kamini T. Bagul 1  · Snehal U. Aouti 1  · Akshay M. Shirsath 1  · Harleen Duggal 1  · Rajesh N. Gacche 2 Received: 22 April 2020 / Accepted: 22 July 2020 © Springer Nature Switzerland AG 2020 Abstract Leishmaniasis is one of the most neglected tropical diseases that demand immediate attention to the identifcation of new drug targets and efective drug candidates. The present study demonstrates the possibility of using threonine synthase (TS) as a putative drug target in leishmaniasis disease management. We report the construction of an efective homology model of the enzyme that appears to be structurally as well as functionally well conserved. The 200 nanosecond molecular dynamics data on TS with and without pyridoxal phosphate (PLP) shed light on mechanistic details of PLP-induced conformational changes. Moreover, we address some important structural and dynamic interactions in the PLP binding region of TS that are in good agreement with previously speculated crystallographic estimations. Additionally, after screening more than 44,000 compounds, we propose 10 putative inhibitor candidates for TS based on virtual screening data and refned Molecular Mechanics Generalized Born Surface Area calculations. We expect that structural and functional dynamics data disclosed in this study will help initiate experimental endeavors toward establishing TS as an efective antileishmanial drug target. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11030-020-10129-8) contains supplementary material, which is available to authorized users. * Rohan J. Meshram rohan@bioinfo.net.in 1 Bioinformatics Centre, Savitribai Phule Pune University, Pune, Maharashtra 411007, India 2 Department of Biotechnology, Savitribai Phule Pune University, Pune, Maharashtra 411007, India