Abstract. The per-residue, gas-phase hydrogen deuterium exchange (HDX) kinetics for individual amino acid residues on selected ion conformer types of the model peptide KKDDDDDIIKIIK have been examined using ion mobility spectrometry (IMS) and HDX-tandem mass spectrometry (MS/MS) techniques. The [M + 4H] 4+ ions exhibit two major conformer types with collision cross sections of 418 Å 2 and 446 Å 2 ; the [M + 3H] 3+ ions also yield two different conformer types having collision cross sections of 340 Å 2 and 367 Å 2 . Kinetics plots of HDX for individual amino acid residues reveal fast-and slow-exchanging hydrogens. The contributions of each amino acid residue to the overall conformer type rate constant have been estimated. For this peptide, N-and C-terminal K residues exhibit the greatest contributions for all ion conformer types. Interior D and I residues show decreased contributions. Several charge state trends are observed. On average, the D residues of the [M + 3H] 3+ ions show faster HDX rate contributions compared with [M + 4H] 4+ ions. In contrast the interior I8 and I9 residues show increased accessibility to exchange for the more elongated [M + 4H] 4+ ion conformer type. The contribution of each residue to the overall uptake rate showed a good correlation with a residue hydrogen accessibility score model calculated using a distance from charge site and initial incorporation site for nominal structures obtained from molecular dynamic simulations (MDS).

Gas-phase hydrogen deuterium exchange (HDX) using D2O reagent and collision cross section (CCS) measurements are utilized to monitor the ion conformers of the model peptide acetyl-PAAAAKAAAAKAAAAKAAAAK. The measurements are carried out in a home-built ion mobility instrument coupled to a linear ion trap mass spectrometer containing electron transfer dissociation (ETD) capabilities. ETD is utilized to obtain per-residue deuterium uptake data for select ion conformers and a new algorithm is presented for interpreting the HDX data. Using molecular dynamics (MD) production data and a hydrogen accessibility scoring (HAS)-number of effective collisions (NEC) model, hypothetical HDX behavior is attributed to various in-silico candidate (CCS match) structures. The HAS-NEC model is applied to all candidate structures and non-negative linear regression is employed to determine structure contributions resulting in the best match to deuterium uptake. The accuracy of the HAS-NEC model is tested with the comparison of predicted and experimental isotopic envelopes for several of the observed c ions. It is proposed that gas-phase HDX can be utilized effectively as a second criterion (after CCS matching) for filtering suitable MD candidate structures. In this study, the second step of structure elucidation 13 nominal structures were selected (from a pool of 300 candidate structures) and each with a population contribution proposed for these ions.

Collision cross section (CCS) measurements with a linear drift tube have been utilized to study the gas phase conformers of a model peptide (Acetyl-PAAAAKAAAAKAAAAKAAAAK). Extensive molecular dynamics (MD) simulations have been conducted to derive an advanced protocol for the generation of a comprehensive pool of in-silico structures; both higher-energy and more thermodynamically-stable structures are included to provide an unbiased sampling of conformational space. MD simulations at 300 K are applied to the in-silico structures to more accurately describe the gas-phase transport properties of the ion conformers including their dynamics. Different methods used previously for trajectory method (TM) CCS calculation employing the Mobcal software [1] are evaluated. A new method for accurate CCS calculation is proposed based on clustering and data mining techniques. CCS values are calculated for all in-silico structures and those with matching CCS values are chosen as candidate structures. With this approach more than 300 candidate structures with significant structural variation are produced; although no final gas-phase structure is proposed here, in a second installment of this work, gas-phase hydrogen deuterium exchange data will be utilized as a second criterion to select among these structures as well as to propose a relative populations for these ion conformers. Here the need to increase conformer diversity and accurate CCS calculation is demonstrated and the advanced methods are discussed.

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As a consequence of the sharing economy attaining more popularity, there has been a shift toward shared-use mobility services in recent years, especially those that encourage users to share their personal vehicles with others. To date, different variants of these services have been proposed that call for different settings and give rise to different research questions. Peer-to-peer (P2P) ride sharing is one such service that provides a platform for drivers to share their personal trips with riders who have similar itineraries. Unlike ride-sourcing services, drivers in P2P ride sharing have their own individual trips to make and are not driving for the sole purpose of serving rider requests. Unlike traditional carpooling, P2P ride sharing can serve on-demand and one-time trip requests. P2P ride sharing has been identified as a sustainable mode of transportation that results in several individual and societal benefits. The core of a P2P ride-sharing system is a ride-matching problem that determines ride-sharing plans for users. This paper reviews the major studies on the operations of P2P ride-sharing systems, with a focus on modeling and solution methodologies for matching, routing, and scheduling. In this paper, we classify ride-sharing systems based on their operational features and review the existing methodologies for each class. We further discuss a number of important directions for future research.