Dr Daniel Cole
Lecturer in Computational Med Chemistry
- Email: email@example.com
I am currently a lecturer in computational medicinal chemistry at the School of Chemistry, Newcastle University. My research is aimed at the application of quantum mechanics to interesting questions in the biological sciences. Used alongside high performance computing, quantum mechanics has the potential to accurately predict physical and chemical properties of systems of hundreds to thousands of atoms. Much of my research is therefore aimed at using large-scale quantum mechanical calculations to develop better models for the description of protein interactions and dynamics, and ultimately for the design of pharmaceutical molecules. I also aim to understand how nature harnesses some of the more exotic characteristics of quantum mechanics to perform a desired function, evidence for which can be found in photosynthetic light-harvesting complexes in plants and bacteria, and even the proteins that transport oxygen around our bodies.
Before taking up my post at Newcastle, I held a Marie Curie international outgoing fellowship, hosted by Prof. William Jorgensen at Yale University and Prof. Mike Payne at the University of Cambridge. I have also previously worked as a research associate at the National University of Singapore and the University of Cambridge.
QualificationsM.Sci. and B.A. in Natural Sciences, University of Cambridge, 2004.
Ph.D. in Physics, Theory of Condensed Matter group, University of Cambridge, 2008.
Large-scale Density Functional Theory
Recent progress in linear-scaling density functional theory (DFT) software allows electronic structure calculations of systems comprising many thousands of atoms to be performed on a routine basis, allowing access to typical length-scales in many biomolecules. Some of the areas in the biological sciences where DFT can play an important role include the energetics of chemical reactions in enzymes, binding of small molecules by metalloproteins, and the parameterisation of model Hamiltonians to describe energy transfer in photosynthetic light-harvesting complexes. Ongoing projects include applications in sustainable energy and medicinal Chemistry.
Computational Drug Design
Optimisation of protein-ligand binding affinity is a central goal of small molecule drug discovery. A wide range of computational methods has been developed for this purpose, but free energy perturbation (FEP) is a particularly attractive option, because it provides a rigorous theoretical means to compute changes in the free energy of binding, limited only by the completeness of the sampling and the accuracy of the force field. Together with researchers in the Jorgensen lab, I have been investigating the use of the replica exchange with solute tempering (REST) enhanced sampling method in the design of inhibitors of HIV reverse transcriptase.
Electronic Structure Analysis
First principles calculations provide a very accurate description of the electronic structure of matter, but the electronic wave function does not provide much chemical insight into the behaviour of the system. We have implemented a range of analysis tools in the ONETEP linear-scaling DFT software to probe the electronic structure of large systems. Natural bond orbital analysis transforms ONETEP's localised basis functions into a set of Lewis-type bonding and lone-pair orbitals to give a chemical picture of bonding. Density derived electrostatic and chemical (DDEC) electron density partitioning produces atom-centred point charges that are chemically intuitive and reproduce the electrostatic potential of the QM calculation.
The room-temperature properties of biological molecules are usually not well-represented by a single structure. We are investigating the use of constrained geometric simulations to generate an ensemble of structures for electronic structure analysis. A particularly interesting application is to light harvesting complexes in which protein dynamics is thought to be a key factor in protecting and generating quantum coherence under laboratory conditions.
- Cole DJ, Janecek M, Stokes JE, Rossmann M, Faver JC, McKenzie GJ, Venkitaraman AR, Hyvönen M, Spring DR, Huggins DJ, Jorgensen WL. Computationally-Guided Optimization of Small-Molecule Inhibitors of the Aurora A Kinase – TPX2 Protein-Protein Interaction. Chemical Communications 2017, 53(67), 9372-9375.
- Fokas AS, Cole DJ, Hine NDM, Wells SA, Payne MC, Chin AW. Evidence of Correlated Static Disorder in the Fenna–Matthews–Olson Complex. Journal of Physical Chemistry Letters 2017, 8, 2350–2356.
- Cole DJ, Hine NDM. Applications of Large-Scale Density Functional Theory in Biology. Journal of Physics: Condensed Matter 2016, 28(39), 393001.
- Cole DJ, Vilseck JZ, Tirado-Rives J, Payne MC, Jorgensen WL. Biomolecular Force Field Parameterization via Atoms-in-Molecular Electron Density Partitioning. Journal of Chemical Theory and Computation 2016, 12(5), 2312-2323.
- Morgan SE, Cole DJ, Chin AW. Nonlinear network model analysis of vibrational energy transfer and localisation in the Fenna-Matthews-Olson complex. Scientific Reports 2016, 6, 36703.
- Fokas AS, Cole DJ, Ahnert SE, Chin AW. Residue Geometry Networks: A Rigidity-Based Approach to the Amino Acid Network and Evolutionary Rate Analysis. Scientific Reports 2016, 6, 33213.
- Cole DJ, Tirado-Rives J, Jorgensen WL. Molecular Dynamics and Monte Carlo Simulations for Protein-Ligand Binding and Inhibitor Design. Biochimica et Biophysica Acta (BBA) General Subjects 2015, 1850(5), 966-971.
- Fokas AS, Cole DJ, Chin AW. Constrained geometric dynamics of the Fenna–Matthews–Olson complex: the role of correlated motion in reducing uncertainty in excitation energy transfer. Photosynthesis Research 2014, 122(3), 275-292.
- Belfield WJ, Cole DJ, Martin IL, Payne MC, Chau P-L. Constrained geometric simulation of the nicotinic acetylcholine receptor. Journal of Molecular Graphics and Modelling 2014, 52, 1-10.
- Cole DJ, Tirado-Rives J, Jorgensen WL. Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering. Journal of Chemical Theory and Computation 2014, 10(2), 565-571.
- Lee LP, Gabaldon Limas N, Cole DJ, Payne MC, Skylaris C-K, Manz TA. Expanding the Scope of Density Derived Electrostatic and Chemical Charge Partitioning to Thousands of Atoms. Journal of Chemical Theory and Computation 2014, 10(12), 5377-5390.
- Kozuska JL, Paulsen IM, Belfield WJ, Martin IL, Cole DJ, Holt A, Dunn SMJ. Impact of Intracellular Domain Flexibility upon Properties of Activated Human 5-HT3 Receptors. British Journal of Pharmacology 2014, 171(7), 1617-1628.
- Lever G, Cole DJ, Lonsdale R, Ranaghan KE, Wales DJ, Mulholland AJ, Skylaris C-K, Payne MC. Large-Scale Density Functional Theory Transition State Searching in Enzymes. Journal of Physical Chemistry Letters 2014, 5(21), 3614-3619.
- Weber C, Cole DJ, O'Regan DD, Payne MC. Renormalization of Myoglobin-ligand Binding Energetics by Quantum Many-body Effects. Proceedings of the National Academy of Sciences of the United States of America 2014, 111(16), 5790-5795.
- Lever G, Cole DJ, Hine NDM, Haynes PD, Payne MC. Electrostatic Considerations Affecting the Calculated HOMO-LUMO Gap in Protein Molecules. Journal of Physics: Condensed Matter 2013, 25(15).
- Lee LP, Cole DJ, Payne MC, Skylaris C-K. Natural Bond Orbital Analysis in the ONETEP Code: Applications to Large Protein Systems. Journal of Computational Chemistry 2013, 34(6), 429-444.
- Lee LP, Cole DJ, Skylaris C-K, Jorgensen WL, Payne MC. Polarized Protein-Specific Charges from Atoms-in-Molecule Electron Density Partitioning. Journal of Chemical Theory and Computation 2013, 9(7), 2981-2991.
- Cole DJ, Chin AW, Hine NDM, Haynes PD, Payne MC. Toward Ab Initio Optical Spectroscopy of the Fenna-Matthews-Olson Complex. Journal of Physical Chemistry Letters 2013, 4(24), 4206-4212.
- Cole DJ, O'Regan DD, Payne MC. Ligand Discrimination in Myoglobin from Linear-Scaling DFT+U. Journal of Physical Chemistry Letters 2012, 3(11), 1448-1452.
- Cole DJ, Rajendra E, Roberts-Thomson M, Hardwick B, McKenzie GJ, Payne MC, Venkitaraman AR, Skylaris C-K. Interrogation of the Protein-Protein Interactions between Human. PLOS Computationsl Biology 2011, 7.
- Cole DJ, Ang PK, Loh KP. Ion Adsorption at the Graphene/Electrolyte Interface. Journal of Physical Chemistry Letters 2011, 2(14), 1799-1803.
- Cole DJ, Skylaris C-K, Rajendra E, Venkitaraman AR, Payne MC. Protein-protein Interactions form Linear-scaling First-principles Quantum-mechanical Calculations. Europhysics Letters Association 2010, 91(3).
- Kubair DV, Cole DJ, Colombi-Ciacchi L, Spearing SM. Multiscale Mechanics Modeling of Direct Silicon Wafer Bonding. Scripta Materialia 2009, 60(12), 1125-1128.
- Cole DJ, Payne MC, Ciacchi LC. Water Structuring and Collagen Adsorption at Hydrophilic and Hydrophobic Silicon Surfaces. Physical Chemistry Chemical Physics 2009, 11, 11395-11399.
- Colombi-Ciacchi L, Cole DJ, Payne MC, Gumbsch P. Stress-Driven Oxidation Chemistry of Wet Silicon Surfaces. Journal of Physical Chemistry 2008, 112(32), 12077-12080.
- Cole DJ, Payne MC, Csanyi G, Spearing SM, Colombi-Ciacchi L. Development of a classical force field for the oxidized Si surface: Application to Hydrophilic Wafer Bonding. Journal of Chemical Physics 2007, 127(20), 204704.
- Cole DJ, Payne MC, Colombi-Ciacchi L. Stress Development and Impurtity Segregation During Oxidation of the Si(1 0 0) Surface. Surface Science 2007, 601(21), 4888-4898.