Samuel Krimm

Bio: Samuel Krimm is an academic researcher from University of Michigan. The author has contributed to research in topics: Polyproline helix & Tripeptide. The author has an hindex of 5, co-authored 8 publications receiving 2644 citations.

Vibrational spectroscopy and conformation of peptides, polypeptides, and proteins.

Abstract: Publisher Summary The vibrational spectrum of a molecule is determined by its three-dimensional structure and its vibrational force field. An analysis of this (usually infrared (IR) and Raman) spectrum can therefore provide information on the structure and on intramolecular and intermolecular interactions. The more probing the analysis, the more detailed is the information that can be obtained. Detailed analyses of the vibrational spectra of macromolecules, however, have provided a deeper understanding of structure and interactions in these systems. An important advance in this direction for proteins came with the determination of the normal modes of vibration of the peptide group in N-methylacetamide, and the characterization of several specific amide vibrations in polypeptide systems. Extensive use has been made of spectra-structure correlations based on some of these amide modes, including attempts to determine secondary structure composition in proteins. Polypeptide molecules exhibit many more vibrational frequencies than the amide modes. Over the years, some normal-mode calculations have provided greater insight into the spectra of particular molecules. However, these have often been based on approximate structures or have employed limited force fields. These force fields can now serve as a basis for detailed analyses of spectral and structural questions in other polypeptide molecules. The aim of this chapter is to present these recent developments in the vibrational spectroscopy of peptides, polypeptides, and proteins.

Potential energy functions: From consistent force fields to spectroscopically determined polarizable force fields

Abstract: We review our methodology for producing physically accurate potential energy func- tions, particularly relevant in the context of Lifson's goal of including frequency agreement as one of the criteria of a self-consistent force field. Our spectroscopically determined force field (SDFF) procedure guarantees such agreement by imposing it as an initial constraint on parameter optimization, and accomplishes this by an analytical transformation of ab initio "data" into the energy function format. After describing the elements of the SDFF protocol, we indicate its implementation to date and then discuss recent advances in our representation of the force field, in particular those required to produce an SDFF for the peptide group. © 2003 Wiley Periodicals, Inc. Biopolymers 68: 383-394, 2003

Spectroscopically Determined Force Field for Water Dimer: Physically Enhanced Treatment of Hydrogen Bonding in Molecular Mechanics Energy Functions

Abstract: Our ab initio transformed spectroscopically determined force field (SDFF) methodology emphasizes, in addition to accurate structure and energy performance, comparable prediction of vibrational properties in order to improve reproduction of interaction forces It is now applied to the determination of a molecular mechanics (MM) force field for the water monomer and dimer as an initial step in developing a more physically based treatment of the hydrogen bonding that not only underlies condensed-phase water but also must be important in molecular-level protein−water interactions Essential electrical components of the SDFF for monomer water are found to be the following: an off-plane charge distribution, this distribution consisting of four off-atom charge sites in traditional lone pair (LP) but also in inverted lone pair (ILP) positions; allowance for a diffuse size to these off-atom sites; and the incorporation of charge fluxes (ie, the change in charge with change in internal coordinate) Parametrizatio

Self-assembly and mineralization of peptide-amphiphile nanofibers

Abstract: We have used the pH-induced self-assembly of a peptide-amphiphile to make a nanostructured fibrous scaffold reminiscent of extracellular matrix. The design of this peptide-amphiphile allows the nanofibers to be reversibly cross-linked to enhance or decrease their structural integrity. After cross-linking, the fibers are able to direct mineralization of hydroxyapatite to form a composite material in which the crystallographic c axes of hydroxyapatite are aligned with the long axes of the fibers. This alignment is the same as that observed between collagen fibrils and hydroxyapatite crystals in bone.

Fourier Transform Infrared Spectroscopic Analysis of Protein Secondary Structures

Abstract: Infrared spectroscopy is one of the oldest and well established experimental techniques for the analysis of secondary structure of polypeptides and proteins. It is convenient, non-destructive, requires less sample preparation, and can be used under a wide variety of conditions. This review introduces the recent developments in Fourier transform infrared (FTIR) spectroscopy technique and its applications to protein structural studies. The experimental skills, data analysis, and correlations between the FTIR spectroscopic bands and protein secondary structure components are discussed. The applications of FTIR to the secondary structure analysis, conformational changes, structural dynamics and stability studies of proteins are also discussed.

The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease.

Abstract: Several variants of the beta amyloid protein, differing only at their carboxy terminus (beta 1-39, beta 1-40, beta 1-42, and beta 1-43), have been identified as the major components of the cerebral amyloid deposits which are characteristic of Alzheimer's disease. Kinetic studies of aggregation by three naturally occurring beta protein variants (beta 1-39, beta 1-40, beta 1-42) and four model peptides (beta 26-39, beta 26-40, beta 26-42, beta 26-43) demonstrate that amyloid formation, like crystallization, is a nucleation-dependent phenomenon. This discovery has practical consequences for studies of the beta amyloid protein. The length of the C-terminus is a critical determinant of the rate of amyloid formation ("kinetic solubility") but has only a minor effect on the thermodynamic solubility. Amyloid formation by the kinetically soluble peptides (e.g., beta 1-39, beta 1-40, beta 26-39, beta 26-40) can be nucleated, or "seeded", by peptides which include the critical C-terminal residues (beta 1-42, beta 26-42, beta 26-43, beta 34-42). These results suggest that nucleation may be the rate-determining step of in vivo amyloidogenesis and that beta 1-42 and/or beta 1-43, rather than beta 1-40, may be the pathogenic protein(s) in AD.

The Use and Misuse of FTIR Spectroscopy in the Determination of Protein Structure

Abstract: Fourier transform infrartd (FTIR) spectroscopy is an established tool for the structural character- ization of proteins. However, many potential pitfalls exist for the unwary investigator. In this review we critically assess the application of FIlR spectroscopy to the determination of protein structure by (1) outlining the principles underlying protein secondary structure determination by FZZR spectroscopy. (2) highhghting the situations in which FZZR spectroscopy should be considered the technique of choice, (3) discussing the manner in which experiments should be conducted to derive as much physiologically relevant information as possible, and (4) outlining current methods for the determination of secondary structure from infrared spectm of proteins,