CHM 825 LECTURE NOTE

Course Information

  • Course Title: Introduction to Computational Chemistry

  • Course Code: CHM 825

Course Synopsis

  • Overview of Computational Chemistry

    • Application of chemical, mathematical, and computing skills to resolve chemical problems using computers.

    • Capabilities include:

      • Calculating molecular geometry (bond lengths, angles, dihedral angles).

      • Estimating energy of molecules at equilibrium and transition states.

      • Evaluating reaction rates and properties (IR, UV-Vis, NMR, etc).

  • Components of Computational Chemistry

    • Molecular mechanics.

    • Ab initio and semi-empirical quantum mechanics.

    • Density functional methods.

    • Molecular dynamics simulations.

    • Predictions prior to experiments to prepare better observations.

Chemo-informatics and Computational Techniques

  • Molecular Modelling

  • Ab initio Molecular Dynamics Techniques

  • Density Functional Theory (DFT)

  • Quantitative Structure-Activity Relationship (QSAR)

  • Drug Design

  • Chemometrics

  • Numerical Methods and Mathematical Modelling

  • Modelling Software

  • Computer Programming Languages

    • C, C++, Java

References

  • A.R. Leach, "Molecular Modelling Principles and Applications", Addison Wesley Longman, 1996.

  • G.H. Grant, W.G. Richards, "Computational Chemistry", Oxford, 1995.

  • F. Jensen, "Introduction to Computational Chemistry", John Wiley & Sons, 1999.

  • J.H. Jensen, "Molecular Modelling Basics", CRC Press, 2009.

  • S.M. Bachrach, "Computational Organic Chemistry", Wiley, 2007.

  • C.J. Cramer, "Essentials of Computational Chemistry Theories and Models (2nd ed.)", Wiley, 2004.

Key Questions Addressed by Computational Chemistry

  1. Mechanistic Questions

  • What intermediates and transition states occur?

  • What factors influence selectivity?

  • Do molecules follow the minimum energy path from reactants to products?

  1. Physical Questions

  • What is the equilibrium geometry of a molecule?

  • How do molecular spectra (IR, UV-vis, NMR) appear and what do they signify?

  1. Conceptual Questions

  • Where are the charges in a molecule?

  • What do the molecular orbitals look like?

  • What stabilizes certain molecules over others?

  • What interactions are important (e.g. hyperconjugative)?

Definitions of Chemoinformatics

  • Chemoinformatics

    • A field integrating design, creation, organization, management, retrieval, analysis, dissemination, visualization, and use of chemical information.

    • Originally defined as transforming data into information and then into knowledge for better decision-making in drug lead identification and optimization.

    • Employs computer science to solve chemical problems.

    • Involves molecular objects in multidimensional chemical space.

  • Evolution of Chemoinformatics

    • Originally focused on chemical structure representation and data manipulation.

    • Has shifted towards exploring extensive chemical databases and discovering new compounds due to advancements in biological data production (e.g., High-Throughput Screening).

The Role of Big Data and Computational Tools

  • Relevance to Chemoinformatics

    • The combination of biological and chemical data necessitates computational tools for data retrieval and analysis.

    • Integrates with computational chemistry, molecular modelling, and drug design.

Computer-Aided Drug Design (CADD)

  • Overview

    • CADD merges applied and theoretical fields to accelerate drug discovery and development processes.

    • Techniques employed include:

      • Virtual Screening

      • Pharmacophore Modelling

      • Molecular Docking

      • Structure-Activity Relationship Modelling

      • Machine Learning approaches.

Computational Chemistry

  • Broad Areas

    • Molecular Mechanics/Molecular Dynamics: Based on classical mechanics principles.

    • Electronic Structure Methods: Based on quantum mechanics principles.

      • Categories:

        • Ab initio methods

        • Semi-empirical methods

Ab Initio Methods

  • Define calculations derived from the theoretical principles based purely on mathematical approximations.

  • Solve the Schrödinger equation for molecular systems, focusing on eigenvalue problems for many-electron molecules.

Schrödinger Equation Complexity

  • Solutions become complex for systems with multiple electrons due to electron-electron repulsion, necessitating approximations.

Born-Oppenheimer Approximation

  • Concept

    • Neglects nuclear kinetic energy in favor of electron dynamics due to mass differences between electrons and nuclei.

    • Allows for effective separation of electronic and nuclear motion, simplifying calculations.

Quantum Mechanics Requirements

  • Wavefunction Representation: Total wavefunction is dependent on electronic and nuclear coordinates.

Hartree-Fock Approximation

  • Overview

    • Central to ab initio methods, calculating the average effect of electron-electron repulsion.

    • Variational nature means calculated energies are greater or equal to exact energies.

    • Utilizes linear combinations of Gaussian-type orbitals to represent wavefunctions.

    • Functions are defined with respect to spatial and angular variables yielding different orbital symmetries.

Determinant and Anti-Symmetry Requirements

  • Electrons must be indistinguishable; satisfies quantum mechanics through antisymmetry in wavefunction.

Hartree-Fock Calculation Process

  • Begins with initial guesses for orbital coefficients, followed by iterative adjustments until convergence is achieved in energy and coefficients.

Method Variants

  • Restricted Hartree-Fock (RHF): Used for singlet spin configurations.

  • Unrestricted Hartree-Fock (UHF): Applicable for systems with unpaired electrons. Introduces potential spin contamination errors.