SBIR-STTR Award

Dysfunction of G protein-coupled receptors (GPCRs) results in diseases as diverse as Alzheimer's, Parkinson's, diabetes, dwarfism, color blindness, retina pigmentosa and asthma. GPCRs are also involved in depression, schizophrenia, sleeplessness, hypertension, impotence, anxiety, stress, renal failure, several cardiovascular disorders and inflammations. Unfortunately, the crystal structure of only a single GPCR (bovine rhodopsin) is known. Therefore, in order to employ structure-based approaches to the design of drugs that target GPCRs, there is a critical need to develop technology that can lead to the production of accurate models of GPCRs. An essential part of constructing accurate GPCR models is the proper treatment of the lipid bilayer membrane. We propose to develop a novel commercial software package capable of performing long length-scale and time-scale molecular dynamics simulations of all-atom GPCR models in coarse grain lipid bilayer/water environments. A recently introduced multi-scale methodology using simplified and computationally efficient coarse-grain representations of lipid bilayers and water in combination with atomistic models for proteins will be further explored and enhanced for modeling GPCRs. The mixed AA-CG methodology will be incorporated into a user-friendly commercial software package directed at pharmaceutical and biotech researchers focusing on discovery and optimization of Class A rhodopsin- like GPCR inhibitors. G protein-coupled receptors (GPCRs) are one of the most important families of target proteins for the development of new medicines; approximately 50-60% of all approved drugs on the market today target GPCRs and nearly all pharmaceutical companies are actively investigating GPCRs. GPCRs are involved in Alzheimer's, Parkinson's, diabetes, dwarfism, color blindness, retina pigmentosa, asthma, depression, schizophrenia, sleeplessness, hypertension, impotence, anxiety, stress, renal failure, cardiovascular disorders, and inflammations. We propose to develop easy-to-use commercial software aimed at producing accurate models for GPCRs that can be used in the design of new medicines that target this important superfamily of proteins.

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Dysfunction of G protein-coupled receptors (GPCRs) results in diseases as diverse as Alzheimer's, Parkinson's, diabetes, dwarfism, color blindness, retina pigmentosa and asthma. GPCRs are also involved in depression, schizophrenia, sleeplessness, hypertension, impotence, anxiety, stress, renal failure, several cardiovascular disorders and inflammations. Unfortunately, the crystal structure of only a single GPCR (bovine rhodopsin) is known. Therefore, in order to employ structure-based approaches to the design of drugs that target GPCRs, there is a critical need to develop technology that can lead to the production of accurate models of GPCRs. An essential part of constructing accurate GPCR models is the proper treatment of the lipid bilayer membrane. We propose to develop a novel commercial software package capable of performing long length-scale and time-scale molecular dynamics simulations of all-atom GPCR models in coarse grain lipid bilayer/water environments. A recently introduced multi-scale methodology using simplified and computationally efficient coarse-grain representations of lipid bilayers and water in combination with atomistic models for proteins will be further explored and enhanced for modeling GPCRs. The mixed AA-CG methodology will be incorporated into a user-friendly commercial software package directed at pharmaceutical and biotech researchers focusing on discovery and optimization of Class A rhodopsin- like GPCR inhibitors. G protein-coupled receptors (GPCRs) are one of the most important families of target proteins for the development of new medicines; approximately 50-60% of all approved drugs on the market today target GPCRs and nearly all pharmaceutical companies are actively investigating GPCRs. GPCRs are involved in Alzheimer's, Parkinson's, diabetes, dwarfism, color blindness, retina pigmentosa, asthma, depression, schizophrenia, sleeplessness, hypertension, impotence, anxiety, stress, renal failure, cardiovascular disorders, and inflammations. We propose to develop easy-to-use commercial software aimed at producing accurate models for GPCRs that can be used in the design of new medicines that target this important superfamily of proteins.

Project Terms:
Active Follow-up; Alzheimer; Alzheimer disease; Alzheimer sclerosis; Alzheimer syndrome; Alzheimer's; Alzheimer's Disease; Alzheimers Dementia; Alzheimers disease; Anxiety; Asthma; Biotechnology; Blood Pressure, High; Bovine Species; Bronchial Asthma; Cardiovascular Diseases; Cattle; Cell Communication; Cell Interaction; Cell-to-Cell Interaction; Cereals; Chemotaxis; Collaborations; Color blindness; Complement; Complement Proteins; Complex; Computer Programs; Computer software; Computing Methodologies; Data; Dementia, Alzheimer Type; Dementia, Primary Senile Degenerative; Dementia, Senile; Development; Diabetes Mellitus; Disease; Disorder; Drug Delivery; Drug Delivery Systems; Drug Design; Drug Formulations; Drug Targeting; Drug Targetings; Drugs; Dwarfism; Dysfunction; Environment; Family; Formulation; Formulations, Drug; Functional disorder; G Protein-Complex Receptor; G-Protein-Coupled Receptors; Goals; Grain; Graphical interface; Homology Modeling; Hydrogen Oxide; Hypertension; INFLM; Idiopathic Parkinson Disease; Impotence; Industry; Inflammation; Insomnia; Insomnia Disorder; Integral Membrane Protein; Intrinsic Membrane Protein; Investigators; Jobs; Kidney Failure; Kidney Insufficiency; Lead; Length; Lewy Body Parkinson Disease; Ligands; Lipid Bilayers; Lipids; Marketing; Medication; Medicine; Membrane; Method LOINC Axis 6; Methodology; Methods; Modeling; Molecular Dynamics Simulation; Msec; Nanism; Nerve Impulse Transmission; Nerve Transmission; Neuronal Transmission; Occupations; Paralysis Agitans; Parkinson; Parkinson Disease; Parkinson's; Parkinson's disease; Parkinsons disease; Pb element; Perception; Pharmaceutic Preparations; Pharmaceutical Agent; Pharmaceutical Preparations; Pharmaceuticals; Pharmacologic Substance; Pharmacological Substance; Physiopathology; Primary Parkinsonism; Primary Senile Degenerative Dementia; Process; Production; Professional Postions; Proteins; Receptor Protein; Renal Failure; Renal Insufficiency; Research; Research Personnel; Research Resources; Researchers; Resolution; Resources; Retina; Rhodopsin; Running; Schizophrenia; Schizophrenic Disorders; Science of Medicine; Scientist; Screening procedure; Sensory; Sleeplessness; Software; Solvents; Speed; Speed (motion); Stress; Structure; System; System, LOINC Axis 4; Technology; Testing; Time; Transmembrane Protein; Validation; Vascular Hypertensive Disease; Vascular Hypertensive Disorder; Visual Purple; Water; base; bovid; bovine; cardiovascular disorder; computational methodology; computational methods; computer methods; computer program/software; cow; dementia of the Alzheimer type; dementia praecox; depression; design; designing; diabetes; disease/disorder; drug candidate; drug development; drug/agent; follow-up; gene product; graphic user interface; graphical user interface; heavy metal Pb; heavy metal lead; hyperpiesia; hyperpiesis; hypertensive disease; impotent; inhibitor; inhibitor/antagonist; interest; lipid bilayer membrane; membrane structure; millisecond; molecular dynamics; neurotransmission; novel; pathophysiology; primary degenerative dementia; receptor; schizophrenic; screening; screenings; senile dementia of the Alzheimer type; simulation; tool; user-friendly; virtual; water environment