Computational Biology

BS123A/MB223

UC-Irvine

Ray Luo, MBB, BS

Syllabus

• Prerequisite: Math 7 and 2D or 2J, Phys 3C, Chem 51C, BS 97, 98 and 99 required; Chem 130A and Chem131A recommended.

• Textbook: Molecular Modelling by Leach; Bioinformatics by Mount• Grading Policy: Letter grade with P/NP option. Grades will be 50%

based on weekly computer lab projects, 25% by mid-term, and 25% by final.

• Computer Labs: A total of seven projects will be assigned. Students will be allowed to make up one missed project outside the lab by prior arrangement with the instructor due to medical or similar emergency.

• Outline: QM v.s. MM, minimization, simulation methods and analysis, pairwise sequence alignment, multiple sequence alignment, sequence database search, protein structure prediction.

Reading Assignment

• Leach, Chapter 1; Mount, Chapter 1.

Scope of Computational Biology

• Bioinformatics: Research, development, or application of computational tools and approaches for expanding the use of biological, medical, behavioral or health data, including those to acquire, store, organize, archive, analyze, or visualize such data.

• Computational Biology: The development and application of data-analytical and theoretical methods, mathematical modeling and computational simulation techniques to the study of biological, behavioral, and social systems.

Scope of This Course

• Development of computational methods

• Application of computational methods to biology

• Focus on molecular biology only

Inputs to Computations

• Sequences and structures

• Experimental information

Theoretical Ground:Classical Mechanics

Building on the work of Galileo and others, Newton unveiled his laws of motion in 1686. According to Newton:

• I. A body remains at rest or in uniform motion (constant velocity - both speed and direction) unless acted on by a net external force.

• II. In response to a net external force, F, a body of mass m accelerates with acceleration a = F/m.

• III. If body i pushes on body j with a force Fij, then body j pushes on body i with a force Fji.

Theoretical Ground:Classical Mechanics

• How to obtain forces?

• Classical mechanics is completely deterministic: Given the exact positions and velocities of all particles at a given time, along with the potential energy V, one can calculate the future (and past) positions and velocities of all particles at any other time.*

• The evolution of the system's positions and momenta through time is often referred to as a trajectory.

Theoretical Ground:Quantum Mechanics

A number of experimental observations in the late 1800's and early 1900's forced physicists to look beyond Newton's laws of motion for a more general theory: Wave had particle-like properties; and particle had wave-like properties. In molecular processes, the quantum effect dominates.

Theoretical Ground:Quantum Mechanics

• Formulation of Shrödinger's wave equation:

• This partial differential equation is difficult to deal with and generally impossible to solve analytically (This is also true for Newton’s equation of motion*). Here is a probability density of the system with. Note that motion is probabilistic.

Theoretical Ground:Quantum or Classical Mechanics or

Statistical Formalisms?

• Ideally we should use quantum mechanics to study molecular events.

• Biomolecules are simply too large to be treated quantum mechanically.

• Sometimes even classical mechanical treatments are too expensive.

• What if no structural information to begin with?

Theoretical Ground:Different Levels of Abstraction

• Studies involving covalent interactions (enzyme reaction): quantum mechanics; extremely slow

• Studies involving noncovalent interactions (conformational references, molecular recognition): classical mechanics; acceptable for a few structures

• Studies involving sequences only: statistical formalisms; extremely fast

Where to know more about quantum mechanics?

• Upper-level physical chemistry in chemistry department

• Upper-level modern physics in physics department

Only classical mechanics and statistical formalisms will be covered

What Problems to Study in Molecular Biology?

• Understanding the molecular mechanisms of biological events of known biomolecules

• Predicting the functions of unknown biomolecules.