CAREER: Development of Non-Additive Lipid Force Fields and Application to the Study of Charged Amino Acid Residues in Lipid Bilayers and the Role of Bilayer-Resident Water

University Of Delaware, Newark DE

Investigators

Abstract

Intellectual Merit Living cells have an inside and an outside, separated by a barrier called the cell membrane, primarily made of fundamental units called lipids. Molecules (such as salts, ions, polar molecules) that are happy (energetically stable) in water are not always happy in a membrane-like environment. Surprisingly, however, numerous water-loving molecules are found in the membrane or are known to cross the membrane environment quite easily. Cell penetrating peptides are observed to readily enter cells. Since water-loving molecules appear to reside within and transfer through the cell membrane, it is natural to think that water goes along for the ride. Water has an important role in these processes. Since it is impossible to see individual water molecules with laboratory experiments, computer programs will be used to perform what are known as molecular simulations. These computational methods, incorporating mathematical descriptions of the physics of how biological molecules interact with one another, follow the motions of individual molecules in time and space. This allows researchers to explore the role of water associated with cell membranes (bilayers) in the transfer of polar and charged molecules through this environment. The view is at the atomic and molecular level! Novel methods will be used that have been developed to describe the varying molecular properties of water and permeating molecules as they move through sharply different environments. The research will address the interaction between water and lipids in the membrane. Specifically, does the water present in the local environment of the permeating molecule support structural changes of the membrane that stabilize the molecule in the "oily" lipid region? More broadly, understanding the role of water in differing environments has implications in numerous scientific and technological contexts (water-mediated self-assembly of nanoparticles, colloidal suspensions and their role in the environment, etc.), thus furthering our global understanding of this ubiquitous solvent and its behavior across different scientifically and technologically important chemical environments. Application of these novel methods on new computer hardware such as Graphical Processing Units (GPU's) that are now becoming viable commodity high-performance computing alternatives for routine computing will be continued. Broader Impacts Motivated by the inescapable current and future requirement for cooperation between the quantitative and qualitative scientific disciplines to further our understanding of fundamental biophysical and biochemical processes, two educational/outreach goals will be established. 1). A multi-disciplinary team consisting of a university professor and two veteran teachers (of chemistry/physics and biology) will introduce students at Newark High School (NHS; which serves a substantial population of minority students and groups underrepresented in science, technology, and engineering) to an introductory computational chemistry course that will emphasize a philosophy of multi-disciplinary approaches, combining the skill sets, tools, and knowledge of the fields of chemistry, biology, physics, math, and computer science, to understanding fundamental biophysical phenomena. This will expose students to practical computer tools and skills widely used in academia and industry. 2). To support the mathematics preparedness of undergraduate chemistry and biochemistry students at the University of Delaware, and to spark greater student interest in the pursuit of research in such fields as biophysics, chemical physics, and computational sciences, an introductory computational chemistry course will be developed, using state-of-the-art computers and programs, focusing on mathematics of chemistry to solve problems of a chemical nature and to prepare students for the mathematical rigor of Physical Chemistry courses. Such extra preparation and opportunities for chemistry students to sharpen their basic math skills will make Physical Chemistry a less burdensome, more enriching (and perhaps fun) experience for students. Project goals serve to increase students' quantitative reasoning skills at an early point in their careers, thus establishing a firm platform from which to pursue numerous avenues of research relevant to future societal needs.