Accurate energy evaluation for peptide hydration

The novel engineering and/or physical sciences content of the research (the science that places it within EPSRC's remit).
This project resorts under the Chemical Sciences Grand Challenge of "Directed Assembly of Extended Structures with Targeted Properties (DAESTP)". Given the longer term impact on proteins, this proposal will fit the priority "Chemical Biology and Biological Chemistry". Furthermore, in the very long term, this proposal is relevant for the grand challenge "Healthcare Technologies". There is a strong Machine Learning component to this project, and thus overlap with Artificial Intelligence, a popular funding topic. The associated scientific product is called FFLUX, which is a completely new force field, designed by novel principles and encoded as a software package.

The research questions the project is trying to address/the objectives of the project;

The main question is how to make molecular dynamics simulations of peptides in water more accurate and reliable in terms of the prediction of structure and dynamics, both against experiment and compared to results from traditional force fields. An overall objective is to incorporate FFLUX into the UKRI-sponsored package DL_POLY (Daresbury lab), and a second objective is to prove that the results obtained by FFLUX are indeed closer to experiment.

More specific objectives are:
o implement the multipolar Ewald method in order to carry out simulations for pure water (in ambient conditions). Polarisation is handled by FFLUX at "monomer level".
o Construct Kriging models for oligomeric water obtained with adaptive sampling.
o Carry out MD simulations with oligomeric water.
o Construct Kriging models of amino acids and small peptides.
o Model the peptide/water interface with Kriging.
o Predict the structure and dynamics peptides in water.

The approach that will be taken to answer these questions (what the student will actually be doing);
This project builds on the results of the EPSRC Fellowship entitled "Reliable computational prediction of molecular assembly". This work has led to a next-generation in-house force field called FFLUX. This force field is much more realistic than a point-charge based force field such as AMBER. Moreover, FFLUX "sees the electrons" and is hence closer to the underlying quantum mechanics that ultimately governs the behaviour of all matter. FFLUX also introduces multipole moments, which is essential for accurate electrostatics. There is a modern and accurate energy partitioning method called Interacting Quantum Atoms (IQA), which offers a step change in the rigour of atomistic energy analysis. IQA is a parameter-free method that is intuitive but, at the same time, very close to the quantum mechanical character of atoms themselves.

The student will be programming in FORTRAN90, interfacing the Ewald method with DL_POLY and FFLUX. He will run molecular dynamics simulations and by careful systematic testing gather unprecedented insight in the behaviour of peptides in water.