What is life? More than 50 years ago, Erwin Schrödinger, cofounder of quantum mechanics in the early 1920s and Nobel Prize Laureate, published a book: What is life? In this book, Schrödinger asked, "How can the events in space and time which take place within the spatial boundary of a living organism be accounted for by physics and chemistry?" In other words, can we study life processes at the very fundamental level of atoms and molecules and by physical and chemical principles? This brilliant idea has inspired generations of scientists, and it has led to many exciting discoveries such as the double helix structure of DNA, which have greatly advanced our understanding in life and life processes.

Today, computer modeling and simulations have become important techniques that assists us in the study of biological cells, functional units, and life processes at the atomic level. Computational chemistry provides a powerful way not only to explain the structures and functions of biological systems but also to predict new relations and effects due to biological design, intervention and mutation. For example, how does genetic information lead to producing of proteins? What controls the signal transduction in the nervous system? How does the influenza virus infect the human body? Why are some of the oral drugs we take not working? Those questions are not only very interesting but also fundamentally important to us.

The research in Dr. Lin's group focuses on the development of new methodology for computer modeling and simulations of complex systems. The methods are applied to address a broad range of problems in chemistry, biochemistry and biophysics.

Method Development

• Combined quantum-mechanical/molecular-mechanical (QM/MM) methods
• Reaction dynamics with multi-dimensional quantum tunneling
• Multi-configuration molecular mechanics (MCMM)
• Many-body expansion for condensed-phase simulations

Applications

• Properties and functionalities of enzymes, ion channels, nanostructures and protein/DNA/RNA complexes
• Highly accurate potential energy, dipole moment, spectroscopy and dynamics for polyatomic molecules and clusters

Chemistry Professor Wins National Science Foundation Career Award

Obtaining a Career Award from the National Science Foundation (NSF) is highly coveted and extremely competitive. Hai Lin, an assistant professor of chemistry, received the Faculty Early Career Development (CAREER) NSF award this spring, the first CAREER award for the College of Liberal Arts and Sciences and the second for the University of Colorado Denver. Lin is now supported by approximately $625,000 to carry out his research titled Multiscale Simulations of Chloride Transport Proteins by Combined Quantum and Classis Mechanical Approaches.

"The CAREER program at the NSF is a prestigious grant program that is aimed at providing five years of funding to outstanding scientists at early stages of their independent career," says Mark Anderson, chair and professor of the chemistry department. "The grant has two components—a research component and an educational component. Hai Lin is a computational chemist whose research focuses on trying to understand chloride transport proteins."

Proteins that form channels and pumps for small molecules and ions across cell membranes are critical for all of life. Failure of such proteins to work properly can cause hereditary diseases such as cystic fibrosis, myotonia (muscle stiffness), renal salt loss, deafness, urinary protein loss, kidney stones, osteoporosis and blindness. Understanding the details of the functioning of such proteins and their molecular dynamics is critical to understanding the mechanisms of movements of ions, such as chloride and protons, across membranes. Rigorous computational analyses of such channels and pumps, and the ions and molecules they move across membranes, is one important approach to understanding how these function and might be regulated, or perhaps corrected in cases of malfunction. This computational approach is what is being funded by NSF.

"Progress made in the research will be integrated directly into the curriculum of my Molecular Modeling and Simulation course," says Lin. "And undergraduate and MS students will participate in the research by doing small subprojects. The research program will be integrated into the LAB COATS (Link to Advanced Biomedical Research Career Opportunities and Training Section) program at UC Denver, the goal of which is to retain undergraduates from underrepresented groups in science and assist them with entry into graduate school and the pursuit of careers in research."

"We are extremely proud that Hai Lin has received a prestigious NSF CAREER research award," says Jim Hageman, associate vice chancellor for research at CU Denver. "His leading-edge contributions in computations of complex molecular structures are being recognized; this award will allow him to advance his work in significant ways and to incorporate new elements of this into his teaching."