Molecular Horizons Seminar - Professor Alan Mark

Despite advances in biophysical techniques it is still not possible to directly observe the energetic and dynamic properties of individual atoms in biomolecular systems using experimental approaches. Everything we think we know regarding biomolecular systems at an atomic level is to some extent a model. The question is to what extent can the models used to interpret experimental data be trusted? While the overall structure of a protein may be resolved in near atomic detail, the position, orientation and/or conformation of a small molecular ligands (cofactors, inhibitors etc.) are often much less certain. Electrostatics are generally ignored in structure refinement. There is also systematic bias in how data is used or interpreted.

The variation in area per lipid in theoretical calculations of membrane systems is much less than that measured experimentally. This is not only a problem for experimentalists but represents a fundamental challenge to theoreticians attempting to validate computational models. Using a range of examples, I will illustrate how theoretical or structural models bias our interpretation of data, and how, when used appropriately, molecular simulations, provide a unique means to challenge our interpretation of experimental data leading to increased certainty in some cases, new insights into the true nature of biomolecular systems in others.