Report of Recommendations to Iowa State University of Science and Technology on the Review of Selected General and Application Controls over the University's Accounts Receivable System, April 6th - May 14th 2004

State University Audit Report

Understanding the two-component sensing System of virulent bacteria

Report for the scientific sojourn carried out at the l’ Institute for Computational Molecular Science of the Temple University, United States, from 2010 to 2012. Two-component systems (TCS) are used by pathogenic bacteria to sense the environment within a host and activate mechanisms related to virulence and antimicrobial resistance. A prototypical example is the PhoQ/PhoP system, which is the major regulator of virulence in Salmonella. Hence, PhoQ is an attractive target for the design of new antibiotics against foodborne diseases. Inhibition of the PhoQ-mediated bacterial virulence does not result in growth inhibition, presenting less selective pressure for the generation of antibiotic resistance. Moreover, PhoQ is a histidine kinase (HK) and it is absent in animals. Nevertheless, the design of satisfactory HK inhibitors has been proven to be a challenge. To compete with the intracellular ATP concentrations, the affinity of a HK inhibidor must be in the micromolar-nanomolar range, whereas the current lead compounds have at best millimolar affinities. Moreover, the drug selectivity depends on the conformation of a highly variable loop, referred to as the “ATP-lid, which is difficult to study by X-Ray crystallography due to its flexibility. I have investigated the binding of different HK inhibitors to PhoQ. In particular, all-atom molecular dynamics simulations have been combined with enhanced sampling techniques in order to provide structural and dynamic information of the conformation of the ATP-lid. Transient interactions between these drugs and the ATP-lid have been identified and the free energy of the different binding modes has been estimated. The results obtained pinpoint the importance of protein flexibility in the HK-inhibitor binding, and constitute a first step in developing more potent and selective drugs. The computational resources of the hosting institution as well as the experience of the members of the group in drug binding and free energy methods have been crucial to carry out this work.

Iowa State Center Business Office, Iowa State University of Science and Technology, Independent Auditor's Reports Financial Statements, June 30, 2003 & 2004

State University Audit Report

Report of Recommendations to Iowa State University of Science and Technology on the Review of Selected General and Application Controls over the Tuition System, April 23 to May 23, 2003

State University Audit Report

Ice Arena Facility Revenue Note Funds, Iowa State University of Science and Technology, Independent Auditor's Report, Financial Statements and Supplemental Information, June 30, 2004

State University Audit Report

Dormitory and Dining Services Revenue Bond Funds, Iowa State University of Science and Technology, Independent Auditor's Report Financial Statements and Supplemental Information, June 30, 2004

State University Audit Report

Academic Building Revenue Bond Funds, Iowa State University of Science and Technology, Independent Auditor's Report Financial Statements and Supplemental Information, June 30, 2004

State University Audit Report

Parking System Revenue Bond Funds, Iowa State University of Science and Technology, Independent Auditor's Reports Financial Statements and Supplemental Information, June 30, 2004

State University Audit Report

Indoor Multipurpose Use and Training Facility Revenue Bond Funds, Iowa State University of Science and Technology, Independent Auditor's Report Financial Statements and Supplemental Information, June 30, 2004

State University Audit Report

Hilton Coliseum Revenue Bond Funds, Iowa State University of Science and Technology, Independent Auditor's Report Financial Statements and Supplemental Information, June 30, 2004

State University Audit Report

Student Health Facility Revenue Bond Funds, Iowa State University of Science and Technology, Independent Auditor's Report Financial Statements and Supplemental Information, June 30, 2004

State University Audit Report

Regulated Materials Facility Revenue Bond Funds, Iowa State University of Science and Technology, Independent Auditor's Report Financial Statements, June 30, 2004

State University Audit Report

Recreational Facility Revenue Bond Funds, Iowa State University of Science and Technology, Independent Auditor's Report Financial Statements and Supplemental Information, June 30, 2004

State University Audit Report

Telecommunications Facilities Revenue Bond Funds, Iowa State University of Science and Technology, Independent Auditor's Report Financial Statements and Supplemental Information, June 30, 2004

State University Audit Report