Sérgio F. Sousa represented BioSIM a the “Protein Simulations – Current State of the Art” Meeting that took place in Telavive, Israel between October 22 and 24, with a communication entitled “Simulating Enzymatic Mechanisms with QM/MM Methods”.
Technological and theoretical development enable researchers to follow on protein dynamics directly by experiments, not only by NMR but also by (sub)terahertz spectroscopy (J Chem Phys 142:055101, 2015) and X-ray free electron lasers (Struct Dynamics 4:044003, 2017). Moreover, stronger synchrotron sources make sub-atomic resolution X-ray crystallography more common (IUCrJ 2:464–474, 2015) whereas room-temperature crystallography sheds light on the dynamics of enzymes (J. Med. Chem., 2018–2025, 2017).
In this workshop, the role of computer simulations of proteins in light of these exciting developments was discussed. The aim of the workshop was to come up with an understanding of what is necessary in order to push the boundaries of the simulations, and enable researchers to provide useful predictions and useful analysis for experimental studies of protein dynamics.
Specific questions addressed in the meeting included:
• What is the current state-of-the-art in terms of force-fields, timescales and enhanced sampling methods?
• How do we improve the modelling of cofactors and metal ions?
• Can we estimate anisotropic displacement factors and the location of hydrogen atoms directly from simulations?
• Where should we put more effort in order to advance the field in the next three years and beyond (improved classical forcefields, polarisable forcefields, coarse grained simulations, enhanced sampling methods, or something else)?