Our Research
Immunophysics. We study the physical basis of immune system
function and regulation.
We explore the structure and dynamics of immune system proteins and how
proteins interact with each other, with their environment, and with small
ligands.
We address fundamental questions such as:
what is the mechanism of
immune system function at molecular and cellular level? What is the mechanism of
immune system regulation and how the immune system discriminates between "self"
and "nonself"? How autoimmune disease relates to failure of immune system
regulation at molecular and cellular level?
Immunoengineering. We use immunophysics knowledge to design
immune system regulators or inhibitors with tailored structural and
physicochemical properties and with desired biological activities.
Our efforts focus on
the design of native and viral regulators of the complement system,
by introducing knowledge-based perturbations in structure, dynamics, interactions,
and eventually function.
We also work on the design of human antibacterial proteins.
Drug Design. We use
structure-dynamics-interactions-function relations to design low-molecular mass
inhibitors of immune system proteins. Many of our targets invovle proteins,
regulators, and receptors of the complement system and their interactions.
Our aim is to develop drugs against autoimmune
diseases and other pathological conditions involving innaproriate
activation/regulation of
the complement system. We also target the interactions of viral proteins with
human receptors, with focus on HIV-1.
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Our Methods
Our methods are computational and spectroscopic, with emphasis in electrostatic
calculations, molecular dynamics simulations, structural bioinformatics,
nuclear magnetic resonance (NMR)
spectroscopy, protein and peptide structure determination and dynamics,
and pharmacophore design. Methodologically, we develop
high-throughput computational protocols for the
calculation of electrostatic similarity indices and free energies,
based on Poisson-Boltzmann electrostatics,
and for clustering analyses of families of homologous proteins and alanine scans.
We also develop quasi-dynamic pharmacophore models, derived from NMR data and
molecular dynamics trajectories.
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Our Research Systems
Some of our active research projects in immunophysics include protein-protein
interactions within the complement system, involving C3 and its fragments C3b,
C3c and C3d, receptors CR1 and CR2, and regulators Factor H, DAF, and MCP.
In addition, we study the catalytic mechanism of
complement serine proteases, such as Factor D, Factor B, C1s, C1r, and C2.
We also work on the structural modeling and dynamics of GPCRs, such as
C3aR, C5aR, CXCR1, and CCR5, and on docking studies with interacting proteins.
Our efforts in immunoengineering involve complement control proteins,
including native receptors and regulators and viral inhibitor proteins
of the pox family. We also work on the anti-bacterial proteins known as
human defensins and on SUMO proteins.
Our efforts on drug design involve peptidic inhibitors of the complement
system. These are peptides of the compstatin family which target C3, and
peptides derived from pro-inflammatory proteins C3a and C5a which target
C3aR and C5aR respectively.
Our goal is to design potent compstatin
analogs and C3aR/C5aR agonists and antagonists.
In addition, we study the effect of
known non-peptidic inhibitors in the structure of serine proteases of the
complement system. The eventual goal of this study is design inhibitors
that will be specific to complement serine proteases, without affecting the
function of broad-range serine proteases.
We also work with peptides derived from the V3-loop of
the HIV-1 glycoprotein gp120 and their interactions with the N-terminal
domain of CCR5. The goal of this study is to design entry inhibitors
against HIV.
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Group Photo
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BioMoDeL Participation in Undergraduate Research Conference
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Bioengineering senior Alex Cheung and bioengineering/biology senior Homero Vazquez participated in SCCUR 2008. This is the annual Southern California Conference for Undergraduate Research. Alex and Homero gave oral presentations on their active research projects. The event was hosted by Cal State, Pomona University on November 22, 2008.
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BioMoDeL Cluster Arrived
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The new BioMoDel LINUX cluster has arrived. This is a Penguin 10-node cluster with an Altus 2650SA master node and 10 Altus 650 compute nodes with dual AMD Opteron processors, Gigabit ethernet, and InfiniBand interconnect technology.
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BioMoDeL participates in Annual Fall Meeting of the Biomedical Engineering Society
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Graduate students Chris Kieslich and Aliana Lopez De Victoria and Professor Dimitrios Morikis
participated in the Annual Fall Meeting of the Biomedical Engineering Society, which took
place in St Louis, MO, in October 1-4, 2008. Chris and Aliana presented posters of their
work and Professor Morikis gave an oral presentation.
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BioMoDeL Students participated in BIC Conference
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Graduate students Aliana Lopez De Victoria and Chris Kieslich and undergraduate student Alex Cheung
presented their research at the 9th UC Systemwide Bioengineering Symposium, organized by our
Bioengineering Department at UCR on June 20-22, 2008. This is the annual conference of the
Bioengineering Institute of California, a multicampus reseacrh unit (MRU). Chris gave a
podium presentation and Aliana and Alex gave presented posters at the Biocomputation, In Silico
& Biosystems Modeling tracks. Dr. Morikis was the Chair of the Scientific Program Subcommittee
and chaired the Biocomputation, In Silico & Biosystems Modeling and New Frontiers tracks
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