Research
at Bio Balance
Specific Capabilities 
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Modeling
ligand-receptor interactions
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Development of 3D
pharmacophores for receptor recognition and activation
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Current Research Areas
Molecular Modeling 
Bio
Balance is currently developing robust protocols for construction of 3D models
of molecules. These strategies include: construction of 3D models of bioactive
molecules with their electronic properties included. This capability impacts on
both the design of bioactive agents and the assessment of their adverse effects
because it allows explicit modeling of these agents with the proteins most
relevant to their mechanism of action.
Biophysical
Properties of Molecules 
Electrostatic
Potentials of Receptors 
Computer Modeling of
Drug-Receptor Interactions
Summary
The increase in the affinity of agonists with
increasing pH, together with experiments using thiol specific reagents,
indicate that G protein coupled receptors contain an ionizable cysteine residue
at the ligand binding site. Since treatments with reducing agents have produced
functional activation and potentiated agonist stimulation, it is likely that
the sulfhydryl influences ligand efficacy and receptor activation. Working
together with Dr. Lester Rubenstein, at Mount Sinai's Department of Physiology
and Biophysics, we have derived a two-state acid-base model and a corresponding
molecular model in order to test the hypothesis that cysteine modulation of
ligand binding is related to ligand efficacy. We show that pH-dependent binding
is correlated with ligand efficacy at the 5HT2A receptor. In general,
efficacy is determined by the preference of a ligand for the base over the acid
form of the receptor. Efficacy is also described as a thermodynamic coupling
free energy between a ligand and the acid and base states of the receptor.
Molecular modeling of the third transmembrane domain containing a conserved
cysteine residue shows that efficacy can be measured as the difference in the
electrostatic interaction energies of a ligand with the acid and base forms of
this receptor model. The cysteine residue provides the largest contribution to
this electrostatic interaction energy difference, and thereby, ligand efficacy.
List of companies and individuals that have collaborated with
Bio Balance:
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Gwathmey, Inc. - www.gwathmey.com/
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CEREP - http://www.cerep.fr/
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DSS Infotech International - http://www.dssinfotech.com/
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Dr. Peter Cherry, CCNY - http://med.cuny.edu/
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Dr. Lester Rubenstein, MSSM, Dept. of Physiology and
Biophysics - http://www.mssm.edu/physbio/
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section
Web Page: http://www.bio-balance.com