Department of Chemistry
Indian Institute of Technology Delhi

Simulating Enzyme Reactions by QM/MM Methods

Dr. Subhendu Roy
Center for Multiscale Simulations Department of Chemistry University of Southern California, USA

Date: November 29th 2017 (Wednesday)
Time: 4 PM
Venue: Committee Room, Chemistry Department, 6th Floor

Enzymes are outstandingly efficient natural catalysts which carry out the essential chemical reactions at the physiologically relevant timescales.1 They catalyze reactions such as water splitting (Photosystem II), N2 reduction (Nitrogenase), C–H bond oxidation (Methane Monooxygenase) which are not only necessary for life but also of great importance in sustainable energy and clean environment. Understanding how enzymes ‘work’ is a fundamentally important problem in biology, which has crucial implications in computational enzyme design. These processes involve the breaking and making of chemical bonds with crucial electron reorganization. Standard classical molecular dynamics methods cannot simulate such processes and it requires quantum mechanical methods. Hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) methods can analyze enzyme reactions and dynamics in atomic details, beyond that achievable by experiments. The origin of enzyme catalysis and its mechanisms remain controversial. In view of this, firstly I shall address the question: do dynamics affect the chemical reactions in enzymes?2 Herein I shall discuss the catalytic reaction of Alcohol Dehydrogenase (ADH) to understand the origin of such effects.3 Secondly I shall describe the mechanism of O2 activation and exploration of hitherto unknown intermediates in Salicylate Dioxygenase (SDO).4 Our study provides answers to many fundamental queries by revealing the unprecedented mechanism of O2 activation and the origin of the unexpected regioselectivity in SDO. Finally future research plans will be briefly discussed.

  1. Nobel Lecture, A. Warshel, Angew. Chem. Int. Ed. 53, 10020-10031 (2014).
  2. A. Warshel and R. P. Bora, J. Chem. Phys. 144, 180901-17 (2016).
  3. S. Roy, P. Schopf and A. Warshel, J. Phys. Chem. B, 121, 6520-6526 (2017).
  4. (a) S. Roy and J. Kästner, Angew. Chem. Int. Ed. 55, 1168-1172 (2016). (b) S. Roy and J. Kästner, Chem. Eur. J. 23, 8949-8962 (2017).

All are cordially invited to attend.
Convener (Seminars)