LSM3241: Bioinformatics and LSM3241: Bioinformatics and Biocomputing Biocomputing Lecture 6: Fundamentals of Molecular Lecture 6: Fundamentals of Molecular Modeling Modeling Prof. Chen Yu Zong Prof. Chen Yu Zong Tel: 6516-6877 Tel: 6516-6877 Email: Email: [email protected][email protected]http:// http:// bidd.nus.edu.sg bidd.nus.edu.sg Room 07-24, level 7, SOC1, Room 07-24, level 7, SOC1, National University of Singapore National University of Singapore
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LSM3241: Bioinformatics and Biocomputing Lecture 6: Fundamentals of Molecular Modeling Prof. Chen Yu Zong Tel: 6516-6877 Email: [email protected] .
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LSM3241: Bioinformatics and LSM3241: Bioinformatics and BiocomputingBiocomputing
Lecture 6: Fundamentals of Molecular ModelingLecture 6: Fundamentals of Molecular Modeling
Protein Surface Determines Its Interaction with Protein Surface Determines Its Interaction with Other Molecules:Other Molecules:
Protein-DNA InteractionProtein-DNA Interaction
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Protein Surface Determines Its Interaction with Protein Surface Determines Its Interaction with Other Molecules:Other Molecules:
Protein-RNA InteractionProtein-RNA Interaction
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Protein Surface Determines Its Interaction with Protein Surface Determines Its Interaction with Other Molecules:Other Molecules:
Protein-Drug InteractionProtein-Drug Interaction Mechanism of Drug Action:
A drug interferes with the function of a disease protein by binding to it.
This interference stops the disease process
Drug Design:
Structure of disease protein is very useful
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Atomic motions in a molecule Atomic motions in a molecule
• Atoms are not rigidly positioned.
• External and internal forces can induce atomic motions.
• Some motions have chemical effect. Movie Show:
Protein transient opening for ligand or drug binding and dissociation:
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Atomic motions in a molecule Atomic motions in a molecule
The effect of motions are described by energy:
Energy measures the ability to do work.
Motion is associated
with energy.
Movie Show:
Protein transient opening for ligand or drug binding and dissociation:
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Types of EnergyTypes of Energy Kinetic energy -- motional energy
Kinetic energy is related to the speed and mass of a moving object. The higher the speed and the heavier the object is, the bigger work it can do.
Potential Energy -- "positional" energy. Water falls from higher ground to lower ground. In physics such a phenomenon is
modeled by potential energy description:
Objects move from higher potential energy place to lower potential energy place.
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Potential Energy Description of Molecular MotionsPotential Energy Description of Molecular Motions A molecule changes from higher potential energy form to lower potential energy
form.
Potential energy is determined by inter-molecular, intra-molecular, and environmental forces
The total energy of motions is: Energy = Stretching Energy + Angle Bending Energy +Torsion Energy + Non-Bonded Interaction Energy
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Molecular Modeling: Molecular Modeling: Basic Interactions and Their ModelsBasic Interactions and Their Models
The stretching energy equation is based on Hooke's law. The "kb" parameter controls the stiffness of the bond spring, while "ro" defines its equilibrium length.
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Molecular Modeling: Molecular Modeling: Basic Interactions and Their ModelsBasic Interactions and Their Models
The stretching energy equation is based on Hooke's law. The "kb" parameter controls the stiffness of the bond spring, while "ro" defines its equilibrium length.
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Molecular Modeling: Molecular Modeling: Basic Interactions and Their ModelsBasic Interactions and Their Models
The bending energy equation is also based on Hooke's law
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Molecular Modeling: Molecular Modeling: Basic Interactions and Their ModelsBasic Interactions and Their Models
The bending energy equation is also based on Hooke's law
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Molecular Modeling: Molecular Modeling: Basic Interactions and Their ModelsBasic Interactions and Their Models
The torsion energy is modeled by a simple periodic function
Why?
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Molecular Modeling: Molecular Modeling: Basic Interactions and Their ModelsBasic Interactions and Their Models
Torsion energy as a function of bond rotation angle.
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Molecular Modeling: Molecular Modeling: Basic Interactions and Their ModelsBasic Interactions and Their Models
The non-bonded energy accounts for repulsion, van der Waals attraction, and electrostatic interactions.
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Molecular Modeling: Molecular Modeling: Basic Interactions and Their ModelsBasic Interactions and Their Models
• van der Waals attraction occurs at short range, and rapidly dies off as the interacting atoms move apart.
• Repulsion occurs when the distance between interacting atoms becomes even slightly less than the sum of their contact distance.
• Electrostatic energy dies out slowly and it can affect atoms quite far apart.
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Molecular Modeling: Molecular Modeling: Basic Interactions and Their ModelsBasic Interactions and Their Models