HT model

HT model. GAD symptoms may reflect excessive 5-HT transmission or overactivity of the stimulatory 5-HT pathways. Patients with SAD have greater prolactin response to buspirone challenge, indicating an enhanced central serotonergic response. The role of 5-HT in panic disorder is unclear, but it may have a role in development of anticipatory anxiety. Preliminary data suggest that the 5-HT and 5-HT2 antagonist meta-chlorophenylpiperazine causes increased anxiety in PTSD patients. 

During the two decades of intense interest in the 1,2-intrastrand d(G pG ) crosslink, the only anti,anti conformation proposed was HH, and only this conformation was expected, before we studied (R,S,S,R)-BipPt(d(GpG)). Remarkably, we found two N(7)-Pt-N(7) crosslink products one was an HH1 conformer, but the other was a new HH conformer (HH2) (Fig. 7). Each product had a pair of H(8) signals with a dispersion (Fig. 8) and a medium H(8)-H(8) NOESY cross-peak, features consistent with HH conformers [38] [63] [67] [68]. The very similar H(8)-H(8) distance, estimated for both in the medium-distance (2.5-3.5 A) range, is consistent with HH bases. For comparison, H(8)-H(8) distances in HT models are 4.5-5.5 A. No H(8)-H(l ) cross-peaks were observed in the 300 ms mixingtime NOESY spectrum, indicating that all of the G s are anti since an intense H(8)-H(l ) cross-peak would be observed for a syn-G. ... 

Hence, in order to obtain the best possible information from CombC, several HTS models must be used in parallel, i.e. MTMMS. 

By doing this it is possible to make a multivariate analysis of the results and obtain information on the discrimination power of the different HTS models. 

V a one-bond-flip (OBF), bicycle-pedal (BP), > Models. The OBT and HT models include... 

Here Ef is the amplitude, t the duration, and co the frequency of the ith pulse. This scheme has been applied in Ref [46] to a generic two-dimensional HT model which incorporated a H-atom reaction coordinate as well as a low-frequency H-bond mode. In a subsequent work [47] the approach has been specified to a simple model of HT in thioacetylacetone. The Hamiltonian was tailored to the form of Eq. (4.1) based on the information available for the stationary points, that is, the energetics as well as the normal modes of vibration. From these data an effective two-dimensional potential was constructed including the H-atom coordinate as well as a coupled harmonic oscillator, which describes the 0-S H-bond motion. Although perhaps oversimplified, this model allowed the study of some principle aspects of laser-driven H-bond motion in an asymmetric low-barrier system. 

One of the first off-lattice minimalist models was developed by Honeycutt and Thirumalai (HT) in 1990 to model a p-barrel motif. It models each amino acid as a single bead like those previously described, but it incorporates much more realistic energetic interactions by accounting for both nearest- and non-nearest-neighbor forces as well as for bond and torsion angles. The HT model includes three different types of residues hydrophobic (B), hydrophilic (L), and neutral (N). Consider the sequence for this 46-residue protein B9N3(LB)4N3B9N3(LB)4L. Its Hamiltonian is as follows. 

The dynamics scheme used for the HT model is different from those previously discussed. Here, Langevin dynamics is used. The Langevin equation for a single particle with position x, is given by... 

Figure 6 (a) The native state of the HT model. Hydrophobic residues are black, hydrophilic residues are gray, and neutral residues are white, (b) Specific heat (Cy) curve and plots of the average fraction of native contacts (Q) and total number of contacts (C) as a function of temperature for the original HT model, (c) Same curves as in (b) for the minimally frustrated Go-model. The original HT model shows a nonspecific transition, whereas the minimally frustrated model displays the signatures of a two-state folder. Adapted From Nymeyer et al. (Ref. 64). 

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