Predicting Peptide Binding Affinities to MHC Molecules Using a Modified Semi-Empirical Scoring Function

The Major Histocompatibility Complex (MHC) plays an important role in the human immune system. The MHC is involved in the antigen presentation system assisting T cells to identify foreign or pathogenic proteins. However, an MHC molecule binding a self-peptide may incorrectly trigger an immune response and cause an autoimmune disease, such as multiple sclerosis. Understanding the molecular mechanism of this process will greatly assist in determining the aetiology of various diseases and in the design of effective drugs. In the present study, we have used the Fresno semi-empirical scoring function and modify the approach to the prediction of peptide-MHC binding by using open-source and public domain software. We apply the method to HLA class II alleles DR15, DR1, and DR4, and the HLA class I allele HLA A2. Our analysis shows that using a large set of binding data and multiple crystal structures improves the predictive capability of the method. The performance of the method is also shown to be correlated to the structural similarity of the crystal structures used. We have exposed some of the obstacles faced by structure-based prediction methods and proposed possible solutions to those obstacles. It is envisaged that these obstacles need to be addressed before the performance of structure-based methods can be on par with the sequence-based methods

Movement control exercise versus general exercise to reduce disability in patients with low back pain and movement control impairment. A randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Non-specific low back pain (NSLBP) in subacute and chronic stages can be treated effectively with exercise therapy. Research guidelines recommend evaluating different treatments in defined subgroups of patients with NSLBP. A subgroup of patients with movement control impairment (MCI) improved significantly on patient specific function and disability in a previous case series after movement control exercises.</p> <p>Methods/Design</p> <p>In a randomised controlled trial (RCT) we will compare the effectiveness of movement control and general exercise in patients with MCI. 106 participants aged 18 - 75 will be recruited in 5 outpatient hospital departments and 7 private practices.</p> <p>Patients randomly assigned to the movement control exercise group will be instructed to perform exercises according to their MCI. The general exercise group will follow an exercise protocol aimed at improving endurance and flexibility. Patients in both groups will receive 9 - 18 treatments and will be instructed to do additional exercises at home.</p> <p>The primary outcome is the level of disability assessed using the patient specific functional scale (PSFS) which links the perceived pain to functional situations and is measured before treatment and at 6 and 12 months follow-up. Secondary outcomes concern low back pain related disability (Roland Morris questionnaire, RMQ), graded chronic pain scale (GCPS), range of motion and tactile acuity.</p> <p>Discussion</p> <p>To our knowledge this study will be the first to compare two exercise programs for a specific subgroup of patients with NSLBP and MCI. Results of this study will provide insight into the effectiveness of movement control exercise and contribute to our understanding of the mechanisms behind MCI and its relation to NSLBP.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN80064281">ISRCTN80064281</a></p