Research
Jump to Research NavigationComputational Biophysics
The Computational Biophysics laboratory of the IPI comprises a multi-disciplinary team whose remit is to utilize in-silico methods to develop a fundamental understanding of drug delivery systems and their interaction with biological membranes with the aim of predicting, optimising, and/or controlling macroscopic properties and behaviour of chemical and pharmaceutical systems on a rational basis.
Molecular (and higher level) modelling and simulation is now becoming a mature technology that is set to enhance the success rate of drug candidates filtering into the pipeline, reduce the time and cost incurred in dosage form development (or even remove this stage entirely from the critical path), and enable the development of well-behaved formulations and robust processes that require minimum intervention.
The laboratory is actively engaged in extending and developing new methods. Our science interests include solids (crystal engineering), soft matter (membranes and colloidal systems) and polymers, as well as process simulation, and we are a leading group in the area of chemical potential/free energy calculations that are so important in predicting properties such as crystal phase behaviour, solubility and partition coefficients.
Contact details
Prof. Jamshed Anwar PhD, Institute of Pharmaceutical Innovation
University of Bradford, West Yorkshire BD7 1DP, UK. Tel. +44 (0)1274 236145
EMail.
Prof Jamshed Anwar, Laboratory Leader
Crystallisation and crystal engineering; Polymorphism and polymorphic phase transformations;
Lipid membranes & drug penetration enhancement;
Phase equilibria; Chemical potential and free energy calculation; Drug/gene delivery through lipid membranes and permeation enhancement
PDRA to be appointed (funded by Unilever)
Molecular transport through model membranes, modelling of skin lipids.
Research Fellow to be appointed
Free energy calculations; Interfacial free energy; nanoparticle stability
Dr Jittima Chatchawalsaisin, Visiting Faculty, Chulalongkorn University, Thailand
Simulation of crystal growth from vapour and solution
Dr Ir. H. de Waard, Visiting Researcher, University of Groningen, The Netherlands
Stability of sold dispersions and nanoparticles.
Mr Shahzeb Khan, PhD student
Manufacture and stability of nanoparticles.
Research Highlights
Molecular simulation of a crystal to crystal phase transformation
Martensitic transformations are of considerable technological importance, a particularly promising application being the possibility of using martensitic materials, possibly proteins, as tiny machines. For organic crystals, however, a molecular level understanding of such transformations is lacking. We have studied a martensitic-type transformation in crystals of the amino acid DL-norleucine using molecular dynamics simulation. The crystal structures of DL-norleucine comprise stacks of bilayers (formed as a result of strong hydrogen bonding) that translate relative to each other on transformation. The simulations reveal that the transformation occurs by concerted molecular displacements involving entire bilayers rather than on a molecule-by-molecule basis. These observations can be rationalized on the basis that at sufficiently high excess temperatures, the free energy barriers to concerted molecular displacements can be overcome by the available thermal energy. Furthermore, in displacive transformations, the molecular displacements can occur by the propagation of a displacement wave (akin to a kink in a carpet), which requires the molecules to overcome only a local barrier. Concerted molecular displacements are therefore considered to be a significant feature of all displacive transformations. This finding is expected to be of value toward developing strategies for controlling or modulating martensitic-type transformations.
Snapshots from the molecular dynamics simulation trajectory
of the transformation of the â-phase of DL-norleucine at 390 K and ambient
pressure. (a) 200 ps, (b) 320 ps, (c) 400 ps, and (d) 500 ps. The system is
periodic in all three dimensions and comprises 800 independent molecules.
The hydrogen atoms have been removed from the molecules to aid structural
clarity. The arrows highlight the bilayer shifts.
J. Anwar*, S. Tuble & J. Kendrick (2007). Concerted molecular displacements in a thermally-induced solid-state transformation in crystals of DL-norleucine, J. American Chemical Society, 129,2542-2547.
For article please click here
Elucidation of the mechanism of action of the penetration enhancer DMSO
Dimethylsulfoxide (DMSO) is an aprotic solvent that has the ability to induce cell fusion and cell differentiation and enhance the permeability of lipid membranes.It is also an effective cryoprotectant. Insights into how this molecule modulates membrane structure and function would be invaluable toward regulating the above processes and for developing chemical means for enhancing or hindering the absorption of biologically active molecules, in particular into or via the skin. We show by means of molecular simulations that DMSO can induce water pores in dipalmitoyl-phosphatidylcholine (DPPC) bilayers and propose this to be a possible pathway for the enhancement of penetration of active molecules through lipid membranes. DMSO also causes the membrane to become floppier, which would enhance permeability, facilitate membrane fusion, and enable the cell membrane to accommodate osmotic and mechanical stresses during cryopreservation.
Water pore formation in a tensionless DPPC bilayer with 27
mol % DMSO after 261.4 ns. Water molecules are shown in cyan, DMSO
in brown, DPPC headgroup and glycerol backbone particles in blue, and
hydrocarbon particles in light gray.
R. Notman, M. Noro, B. O’Malley & J. Anwar* (2006) Molecular basis for dimethylsulfoxide (DMSO) action on lipid membranes, Journal of the American Chemical Society, 128, 13982-13983.
Asymmetric growth in polar crystals
The growth of crystals of a-resorcinol from the vapor phase is asymmetric alongthe polar axis. By means of molecular-dynamics simulations, the slower growth at the (011) polar surface is traced back to conformational change of the molecule and to surface reconstruction, which may be a general phenomenon in polar crystals.
Snapshot of the equilibrated crystal slab of a-resorcinol,
showingthe marked asymmetry in the crystalline order at the polar
surfaces (01¯1¯ ) and (011).
J.Anwar*, J. Chatchawalsaisan, J. Kendrick, & S.C. Tuble (2007), Asymmetric Crystal Growth of Resorcinol from the Vapor Phase: Surface Reconstruction and Conformational Change are the Culprits, Angewandte Chemie Int. Ed.
