Water at Molecular Interfaces: Structure and Dynamics Near Biomolecules and Amorphous Silica

WATER AT MOLECULAR INTERFACES: STRUCTURE AND DYNAMICS NEAR BIOMOLECULES AND AMORPHOUS SILICA DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Ali A. Hassanali, M.S. Biophysics Graduate Program The Ohio State University 2010 Dissertation Committee: Professor Sherwin J. Singer, Adviser Professor Dongping Zhong Professor Terrence Conlisk Professor Justin Wu ABSTRACT Water, the fundamental constituent of life, has been found to have a critical role at both organic and inorganic surfaces. The properties of water near surfaces, is known to be different from water far away from the interface. This dissertation explores the degree to which inorganic materials such as amorphous silica (glass) and biomolecular surfaces change the properties of water. Of particular interest is the interplay between biological molecules - proteins and nucleic acids - and their aqueous environment, and how this determines biological function. The mobility of water near protein surfaces has been of considerable recent interest. There have been many reports in the literature postulating that interfacial water is incapable of undergoing rapid rotational motions due to strong electrostatic forces from the protein surface. This has led to confusing and conflicting interpre- tations on the molecular origin of the slow features observed in certain experiments that probe protein surfaces. Our theoretical studies resolve the conflicts and show that the slow dynamics observed, originates from the protein and water jostling in a concerted fashion. Our studies support a change in the paradigm for the function of proteins to include both the protein and the surrounding water as active participants in biological function. ii For 80 years, scientists have employed models in which ions and water near the silica surface form a stagnant layer called the Stern layer. To account for all exper- imental features, these models invoke puzzling properties such as the transport of ions through immobile water. In this dissertation, we develop a realistic theoretical description of the water-amorphous silica interface. We have successfully constructed and validated a model for the water-amorphous silica interface and have begun to examine the fate of biomolecules near this important interface. Our simulations chal- lenge the classical textbook Stern layer model. Both ions and water exhibit a sub- stantial degree of mobility, yet the phenomena the Stern layer was originally invoked to explain, are reproduced by our calculations. Theoretical studies for the repair of DNA bases damaged by sunlight demonstrate that fast water motions are critical in ensuring the rapid repair of the bases. We have constructed a simple model using our ground state calculations that provides new insights into the mechanisms of efficient DNA repair that might be deployed in the active site of the DNA repair protein. The splitting energetics during DNA repair is shown to modulate the charge recombination process and can significantly affect the quantum repair yields. iii Dedicated to humanity, in the quest for the search of truth and purpose in this universe iv ACKNOWLEDGMENTS I have always been fascinated and some might say, obsessed with epistemological methods that we think help us understand more about our purpose and role in this complex universe - that is of course, if there is any purpose at all! The original moti- vation for pursuing a PhD in the sciences was and still is motivated by philosophical interests in the scientific method and its intimate connections with other methods of discovery. The journey has been extremely rewarding and in many ways very hum- bling. The beauty of knowledge, is that it manifests itself in an infinite manner in both breadth and depth...and hence I see this milestone as simply the beginning of unending journey. I feel very humbled to be in this position of privilege writing an acknowledgment for my PhD dissertation. I interpret it as a privileged position because circumstances in my life have shaped and facilitated my choices to be where I am. While the PhD degree can often give you an elevated position amongst the academic elite, the “ivory tower” can also be very indifferent to issues of socio-economic justice. Approximately 1 billion people entered the 21st century unable to read or sign their names. I put this fact out as a call for all of us in this privileged position, including myself, to think about and hopefully render progressive responses. I was extremely lucky to have my PhD co-advised by a theoretician and experi- mentalist. The collaboration was very enjoyable and allowed me to get involved in v several projects that were intellectually rewarding. Since this is an acknowledgment, it would be prudent to share some personal experiences about the people you spend so much time with in the office and on email. I’d like to begin by thanking Sherwin for being a phenomenal adviser and more importantly a patient teacher throughout my tenure in the PhD program. Sherwin was always ready to explain things repeatedly to me with a smile on his face. I was always fascinated by his unique skill of taking verbal arguments and expressing them in terms of mathematical equations. He is a very careful scientist (and that’s rare to find these days) who pays close attention to detail that others often neglect. Anyone who spends enough time with Sherwin knows that he has an interesting sense of humor and always lightens the often scientifically intense moments. His intellectual and moral support throughout my PhD was invaluable. I was lucky to have an adviser like Sherwin who loved to argue and debate and who was perfectly comfortable with his students challenging his scientific opinions. Beyond his scientific mentoring, Sherwin always showed a genuine interest and concern in my personal development. Sherwin, I look forward to receiving many more emails from you in the future at 4.30 AM! I’d also like to specifically thank you for taking the time to carefully read, edit and re-write my lousy first drafts of manuscripts. I’d like to thank Dongping for providing fertile ground for a healthy and productive collaboration between theory and experiment on several projects and for being a great co-adviser. Dongping always set the bar very high for both scientific productivity and work ethic. His enthusiasm and excitement for science can often be very contagious! I’ve always been intrigued by Dongping’s ability to choose biological systems that are rich in fundamental physical and chemical problems that in turn provide a lot of room vi for the development of interesting theory and computational work. Dongping has a unique skill of finding voids in scientific arguments, when you think you completely understand all the issues. I am anxious to see what new biological problems you aim to to tackle in the future, for inspiration perhaps, on the development of new computational methods. A special thanks goes to the members of my thesis committee, Terry Conlisk and Justin Wu for carefully reading my thesis and providing insightful comments. I’ve been blessed with a beautiful family who have supported me in a multitude of ways throughout my life. My parents, for giving me the opportunity to pursue further education in the United States, much to the concerns of my darling mother who wanted me much closer to home! My mom and dad provided an environment that allowed for creative exploration of intellectual thought but more importantly, taught me that this must always be accompanied by a profound sense of humility and responsibility. I’d like to thank my sisters Rumina and Raabia for setting the bar pretty high right from the beginning. You left big shoes to fill. Rumina, I guess you will always be the doctor who actually makes a difference! I’d like to thank my three little nieces Imaan, Sahar and Layla for making my Saturday and Sunday mornings entertaining with their singing during many many skype conversations! I’d like to thank my inlaws for all their support in the last 2 years. Living far away from family, friends often become an intricate part of your support system and in many ways take the role as surrogate family members. I’d like to begin my thanking Daniel for being an awesome flatmate for my first two years at OSU. I worked extremely hard my first two years, probably the hardest throughout my PhD, and Daniel was extremely patient with me. I will always have fond memories vii of our philosophical exchanges. Its been a real pleasure sharing different parts of the evolution of my existential identity with you. I’d like to thank Kashif for really being like an older brother to me and looking after me like one of his own family members. I’ve thoroughly enjoyed all our conversations on numerous topics and look forward to many more in the future. I will always remember feeling a sense of relief, every time I’d get a phonecall from you in the evenings after being in the office for over 12 hours. I will also miss our racquetball games...its been a lot of fun! Thanks to Taqdees for playing a motherly role and feeding a hungry and tired graduate student on too many occasions! Laura, I’d like to thank you for not giving up on me, earlier on in our friendship and for dealing with my social idiosyncrasies in a way that was nurturing. I have fond memories of our jogging sessions late at night and the few racquetball games that I destroyed you on! I am really excited about hearing and listening to the unfolding of the bright future that I think lies ahead for you.

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