CEPCEB Members

Dimitrios Morikis Professor Department of Bioengineering University of California, Riverside Riverside , CA 92521 Phone: (951) 827-2696 Fax: (951) 827-5696 Group Website: http://www.engr.ucr.edu/~dmorikis     Areas of Expertise Computational molecular biology Biomolecular structure, dynamics, electrostatics, and interactions Immunophysics Rational peptide, protein, and drug design Structural bioinformatics NMR spectroscopy

Background Current Research Interests Selected Publications (Bibliography Page) Current Laboratory Personnel

Background:

I received my B.S. in physics from the Aristotle University of Thessaloniki, Greece. I came to the US for graduate studies with a Fulbright fellowship and I received my M.S. and Ph.D. degrees in physics from Northeastern University, Boston. For my dissertation I worked in the laboratory of Paul Champion, where I was trained in biophysics, using resonance Raman scattering and other optical methods for the study of heme proteins in solution and crystal states and in room and cryogenic temperatures. For my postdoctoral fellowship I joined the laboratory of Peter Wright at the Department of Molecular biology of The Scripps Research Institute, La Jolla, where I was trained in structural biology, using nuclear magnetic resonance (NMR) methods for the study of the plant protein leghemoglobin and peptides. I have also received a senior NIH postdoctoral award to acquire training in computational chemistry and joined the group of Andy McCammon at the Department of Chemistry and Biochemistry of the University of California, San Diego, where I worked on electrostatic calculations for the study of proton transfer and pH-dependent conformational transitions and catalysis. In 2001, I joined the Department of Chemical and Environmental Engineering of the University of California, Riverside, as a research faculty member, where I initiated programs in immunophysics, peptide and protein design, and drug discovery. In 2006, I joined the newly established Department of Bioengineering at the University of California, Riverside as a professor, where I continue my previous research endeavors with an emphasis on immune system function, regulation, and inhibition. I have also launched new initiatives in plant science.

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Current Research Interests

We follow a cross-disciplinary theoretical and experimental approach, involving biophysics, structural biology, computational chemistry, structural bioinformatics, and bioengineering. Our goals are: (i) to determine structure-dynamics-interactions-function relations for peptides, proteins, protein fragments, and protein complexes, which address basic biological processes; (ii) to design peptides and small proteins with tailored properties and to determine their structure; (iii) to perform rational design for potential therapeutic agents, and (iv) to design de novo peptides of specific structural propensities. Our work is based on the exploration of the dynamic and electrostatic properties of biomolecules and biomolecular complexes using computational methods. We also use nuclear magnetic resonance methods for peptide and protein structure determination.

Proteins are dynamic systems, which interact with their surrounding environment. Proteins participate in a wide range of motions and their dynamics are essential for function. Proteins interact with solvent molecules, other proteins, nucleic acids, ligands, prosthetic groups, carbohydrates, lipids, metals, ions, and small molecules. We use molecular dynamics simulations based on the solution of Newton ’s equation of motion to explore the dynamic properties of peptides, proteins, and protein complexes, such as flexibility, mobility, correlated motions, conformational transitions, and folding.

Electrostatics plays a significant role in secondary, tertiary, and quaternary structure formation and stability. Electrostatics also plays a significant role in recognition and binding for the formation of protein complexes and multi-component assemblies. We use computational methods based on the solution of the Poisson-Boltzmann equation to explore the electrostatic properties of peptides, proteins, and protein complexes, such as ionization states, desolvation, Coulombic interactions, proton sharing and transfer, conformational transitions, stability, and association.

Knowledge of biomolecular structure is the starting point for computational studies at atomic resolution, involving dynamics, electrostatics, thermodynamics, kinetics, and association, which in turn are essential for basic understanding of the physicochemical properties of underlying function. Structure is also the basis of our design efforts for peptides, proteins, and potential therapeutics. We use high-resolution NMR spectroscopy and restrained molecular dynamics-based simulated annealing methods to determine the structure of peptides and small proteins. We also use structural homology methods to model protein structures based on previously solved homologous structures and deposited at the Protein Data Bank. The aim of our structural bioinformatics efforts is to classify proteins according to the spatial distribution of their electrostatic properties, using a combination of structural homology, electrostatic calculations, and similarity indices.

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Selected Publications (Bibliography Page)

Current Laboratory Personnel

• Buddhadeb Mallik, Staff Research Associate
• Jayalakshmi Sridhar, Visiting Assistant Researcher
• Li Zhang, Doctoral Student
• Alexander Cheung, Undergraduate Student

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