Computational Chemistry Program

Software Library

The Molecular Research Institute maintains a large library of diverse software packages embodying a spectrum of state-of-the-art computational methods that enables computers to be the laboratory for scientists to effectively address the multiple aspects of computer-aided design of bioactive agents, construction of 3D models of proteins, macromolecular modeling structure-based inhibitor design and computer-aided risk assessment. The library of programs span many useful methods and procedures from first principles quantum mechanical packages to molecular mechanics and molecular dynamic simulation programs and also include low and high resolution graphics programs.

A careful selection process and continued evaluation of current components and contemplated additions to our software library is an important on-going activity at the Molecular Research Institute.

Specific Capabilities

• Characterization of conformational profiles of bioactive agents by validated search strategy.
• Calculation of electronic and physical properties of analogs.
• Modeling chemical/biochemical reactions.
• Characterization of spectroscopic properties.
• Development of 3D Pharmacophores for receptor recongition and activation.
• Lead optimization by calculation of properties related to drug delivery and enhanced activity.
• Explicit characterization of ligand-protein complexes.
• Optimization and molecular dynamics simulations of proteins and lipid bilayers.
• Construction and assessment of 3D models of proteins.

Current Research Areas

• Interdisciplinary computer-aided design and optimization of CNS active therapeutic agents.
• Design of peptidomimetics.
• Computer-aided risk assessment.
• Evaluation of toxic product formation.
• Determination of properties leading to toxic response.
• Enzyme-inhibitor modeling and design of inhibitors.
• Substrate-enzyme modeling and prediction of product distribution.
• Effect of mutations on enzyme functions.
• Construction of 3D models of proteins.

Experimental Program

The Molecular Research Institute uses state-of-the-art methods for the pharmacological evaluation of CNS active drugs. Our trained professionals are qualified to optimize, adapt, or extend the protocols used to Novel systems. Research in diverse areas of pharmacology is performed that relates the in vitro pharmacology to in vivo behavioral responses.

Specific Techniques Used

The in vitro Pharmacology Program includes:

• Detailed receptor binding studies and mathematical analysis using proprietary (Affinity Analysis) software:
  • Detect Receptor Heterogeneity
  • Assess Ligand Receptor Selectivity

• In Vitro measures of activity:
  • Ion Flux
  • cAMP, Ca2+, PI

• In Vivo Pharmacology includes studies of:
  • Analgesics
  • Anxiolytics
  • Anticonvulsants
  • Sedatives/Hypnotics
  • Cognitive Enhancers
  • Ventilatory Depression
  • Physical Dependence Liability

Current Research Areas

1. Pharmacology of Various Receptor Systems, including:
   • BDZ/GABAA
   • Adrenergic
   • Opioid Receptors
   • Cannabinoid Receptors

2. Neurodevelopment